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PubMed1988

Preliminary crystallographic data, primary sequence, and binding data for an anti-peptide Fab and its complex with a synthetic peptide from influenza virus hemagglutinin.

X-ray quality crystals which diffract to high resolution (less than or equal to 1.9-2.1 A) have been grown of an anti-peptide Fab and its complex with a 9-residue peptide antigen. Both crystals are monoclinic P2(1), with unit cell dimensions a = 90.3 A, b = 82.9 A, c = 73.4 A, beta = 122.5 degrees for the native Fab and a = 63.9 A, b = 73.0 A, c = 49.1 A, beta = 120.6 degrees for the complex. The peptide sequence corresponds to residues 100-108 of all influenza virus hemagglutinins (HA1) of the H3 subtype (1968-1987). The peptide antigen has been well characterized immunologically (Wilson, I.A., Niman, H.L., Houghton, R.A., Cherenson, A.R., Connolly, M.L., and Lerner, R.A. (1984) Cell 37, 767-778; Wilson, I.A., Bergmann, K.F., and Stura, E.A. (1986) in Vaccines '86 (Channock, R.M., Lerner, R.A., and Brown, F., eds) pp. 33-37, Cold Spring Harbor Laboratory, Cold Spring Harbor, NY), structurally, as a free peptide by NMR (Dyson, J.H., Cross, K.J., Houghton, R.A., Wilson, I.A., Wright, P.E., and Lerner, R.A. (1985) Nature 318, 480-483; Dyson, J.H., Lerner, R.A., and Wright, P.E., (1988) Annu. Rev. Biophys. Chem. 17, 305-324), as part of the intact antigen by x-ray crystallography (Wilson, I.A., Skehel, J.J., and Wiley, D. C. (1981) Nature 289, 366-373) and by binding studies to the HA molecule (White, J.M., and Wilson, I.A. (1987) J. Cell Biol. 105, 2887-2896). Knowledge of the three-dimensional structure of the complex will elucidate the details of how anti-peptide antibodies recognize a small peptide antigen and provide insights into the recognition of the same sequence in the intact protein antigen. As both native Fab and the peptide-Fab complex have been crystallized, we can also determine in addition whether changes in the structure of the antibody accompany antigen binding. The nucleotide sequence of the mRNA coding region of the anti-peptide Fab has been determined to provide the amino acid sequence ultimately required for the high resolution three-dimensional structure determination.

Amino Acid Sequence↗
PubMed2000

Five-membered ring formation in unimolecular reactions of peptides: a key structural element controlling low-energy collision-induced dissociation of peptides.

Unimolecular fragmentation reactions of peptides in low-energy collision-induced dissociation are reviewed in the mechanistic context of five-membered ring formation. This structure of intermediates or of fragment ions is recognized as a key element that governs unimolecular peptide fragmentation within the structural framework determined by the peptide backbone and its side-chains. A collection of collision-induced dissociation reactions is presented covering (i) b-ion formation, (ii) the fragmentation of N-terminally acylated peptides, (iii) neutral loss of the C-terminal amino acid in alkali or silver cationized peptides, (iv) the fragmentation of isoAsp-containing peptides and (v) the fragmentation of negatively charged Asp- or Glu-containing peptides. It appears that for all possible nucleophile-electrophile interactions leading to a five-membered ring structure an associated unimolecular peptide fragmentation reaction can be observed.

Amino Acid Sequence↗
PubMed2006

T7 lytic phage-displayed peptide libraries exhibit less sequence bias than M13 filamentous phage-displayed peptide libraries.

We investigated whether the T7 system of phage display could produce peptide libraries of greater diversity than the M13 system of phage display due to the differing processes of lytic and filamentous phage morphogenesis. Using a bioinformatics-assisted computational approach, collections of random peptide sequences obtained from a T7 12-mer library (X(12)) and a T7 7-mer disulfide-constrained library (CX(7)C) were analyzed and compared with peptide populations obtained from New England BioLabs' M13 Ph.D.-12 and Ph.D.-C7C libraries. Based on this analysis, peptide libraries constructed with the T7 system have fewer amino acid biases, increased peptide diversity, and more normal distributions of peptide net charge and hydropathy than the M13 libraries. The greater diversity of T7-displayed libraries provides a potential resource of novel binding peptides for new as well as previously studied molecular targets. To demonstrate their utility, several of the T7-displayed peptide libraries were screened for streptavidin- and neutravidin-binding phage. Novel binding motifs were identified for each protein.

Amino Acid Sequence↗
PubMed2006

Tandem electrospray mass spectrometric studies of proton and sodium ion adducts of neutral peptides with modified N- and C-termini: synthetic model peptides and microheterogeneous peptaibol antibiotics.

The fragmentations of [M+H]+ and [M+Na]+ adducts of neutral peptides with blocked N- and C-termini have been investigated using electrospray ion trap mass spectrometry. The N-termini of these synthetically designed peptides are blocked with a tertiarybutyloxycarbonyl (Boc) group, and the C-termini are esterified. These peptides do not possess side chains that are capable of complexation and hence the backbone amide units are the sole sites of protonation and metallation. The cleavage patterns of the protonated peptides are strikingly different from those of sodium ion adducts. While the loss of the N-terminal blocking group occurs quite readily in the case of MS/MS of [M+Na]+, the cleavage of the C-terminal methoxy group seems to be a facile process in the case of MS/MS of [M+H]+ * Fragmentation of the protonated adducts yields only bn ions, while yn and a(n) ions are predominantly formed from the fragmentation of sodium ion adducts. The a(n) ions arising from the fragmentation of [M+Na](+) lack the N-terminal Boc group (and are here termed a(n)* ions). MS/MS of [M+Na]+ species also yields b(n) ions of substantially lower intensities that lack the N-terminal Boc group (b(n)*). A similar distinction between the fragmentation patterns of proton and sodium ion adducts is observed in the case of peptides possessing an N-terminal acetyl group. An example of the fragmentation of the H+ and Na+ adducts of a naturally occurring peptaibol from a Trichoderma species confirms that fragmentation of these two ionized species yields complementary information, useful in sequencing natural peptides. Inspection of the isotopic pattern of b(n) ions derived from [M+H]+ adducts of peptaibols provided insights into the sequences of microheterogeneous samples. This study reveals that the combined use of protonated and sodium ion adducts should prove useful in de novo sequencing of peptides, particularly of naturally occurring neutral peptides with modified N- and C-termini, for example, peptaibols.

Amino Acid Sequence↗
PubMed1993

Interaction of heme with amphiphilic peptides: use of hemin-CN to probe the interaction of calmodulin with its target peptides.

UNLABELLED: The interaction of heme with several amphiphilic peptides has been studied by absorption and fluorescence spectroscopy. The binding can be followed by the changes in the absorption spectrum of the heme group or by the decrease in the peptide tryptophan fluorescence due to energy transfer to the heme. Despite their small size, ranging from 26 residues for melittin to 14 for mastoporan, a high affinity for heme-CO and hemin-CN (Kd < 100 nM) may be observed. Spectral shifts in the absorption peaks and appreciable geminate recombination after photodissociation of CO from the complex peptide-heme-CO suggest the formation of a heme pocket, as for the natural heme proteins. APPLICATION: hemin-CN can be used as a probe for the interaction of calmodulin with these target peptides. Amphiphilic peptides such as melittin bind to calmodulin with a high (nM) affinity. While both the peptide and calcium-bound calmodulin bind heme-CO, only the peptide binds hemin-CN. These interactions permit studies of the competition between hemin-CN and calmodulin for binding to the peptide: while hemin-CN quenches the melittin tryptophan fluorescence, addition of calmodulin to the [melittin*hemin-CN] complex displaces the hemin-CN and the melittin tryptophan fluorescence is recovered.

Amino Acid Sequence↗
PubMed2000

An automated prediction of MHC class I-binding peptides based on positional scanning with peptide libraries.

Specificities of three mouse major histocompatibility complex (MHC) class I molecules, Kb, Db, and Ld, were analyzed by positional scanning using combinatorial peptide libraries. The result of the analysis was used to create a scoring program to predict MHC-binding peptides in proteins. The capacity of the scoring was then challenged with a number of peptides by comparing the prediction with the experimental binding. The score and the experimental binding exhibited a linear correlation but with substantial deviations of data points. Statistically, for approximately 80% of randomly chosen peptides, MHC-binding capacity could be predicted within one log concentration of peptides for a half-maximal binding. Known cytotoxic T-lymphocyte epitope peptides could be predicted, with a few exceptions. In addition, frequent findings of MHC-binding peptides with incomplete or no anchor amino acid(s) suggested a substantial bias introduced by natural antigen processing in peptide selection by MHC class I molecules.

Animals↗
PubMed1998

An HLA-binding-motif-aided peptide epitope library: a novel library design for the screening of HLA-DR4-restricted antigenic peptides recognized by CD4+T cells.

Susceptibility to a series of autoimmune diseases is strongly associated with particular HLA class II alleles. Identification of T cell clones and antigenic epitopes bound by HLA class II molecules involved in autoimmune diseases is critical to understanding the etiology of these HLA class II-associated diseases. However, establishment of T cell clones in autoimmune diseases is difficult because the antigenic peptides are unknown. Peptide library methods which include all possible peptide sequences offer a potentially powerful tool for the detection of cross-reactive antigenic peptides recognized by T cells. Here, we reduced the number of peptides per mixture by utilizing the known binding motifs of peptides for the HLA-DRB1*0405 molecule and evaluated the effectiveness of this library design. Each library mixture evoked a strong proliferative response in the unprimed peripheral blood lymphocytes (PBL) from HLA-DRB1*0405-positive donors but little or no response in the PBL from HLA-DRB1*0405-negative donors. The library also detected antigenic peptides that activated three antigen-specific T cell lines restricted by HLA-DRB1*0405, with different specificities. The motif-based approach thus presents a powerful method for monitoring T cells in large, heterogeneous T cell populations and is useful for the identification of the mimic peptide epitopes of T cell lines and clones.

Amino Acid Sequence↗
PubMed1971

Number and types of peptide chains in thyroglobulin: tryptic peptides of noniodinated hog thyroglobulin.

In order to identify the number and types of peptide chains in thyroglobulin, noniodinated 19-S thyroglobulin obtained from goitrogen-treated hogs was exhaustively digested with trypsin (EC 3.4.4.4) after reduction and S-carboxymethylation. The digestion mixture was preliminarily separated into 30 fractions on Sephadex G-100 or G-15 and SE-Sephadex columns. The number of various tryptic peptides contained in each fraction was determined on peptide maps, where spots were detected with ninhydrin for total peptides and with each specific reagent for arginine, histidine or tyrosine-containing peptides. The number of total peptides observed in most of the fractions was estimated to be half the number of lysine plus arginine residues found in each fraction per mole of thyroglobulin, and the number of specific peptides was also close to half the number of each specific amino acid. These findings imply that thyroglobulin has 2-fold symmetry in the structure at the level of tryptic fragments and thus probably at the level of intact peptide chains.

Amino Acids↗
PubMed1987

Competition of a growth stimulating-/cholecystokinin (CCK) releasing-peptide (monitor peptide) with epidermal growth factor for binding to 3T3 fibroblasts.

The growth stimulating-/cholecystokinin (CCK) releasing-peptide (monitor peptide) is a peptide purified from rat bile-pancreatic juice on the basis of its stimulatory activity toward pancreatic enzyme secretion. Its multiple functions and peptide sequence suggested that it is distinct from epidermal growth factor (EGF). However, we found that the peptide competes with [125I]-EGF in the binding to Swiss 3T3 fibroblast cells to almost the same extent as unlabeled EGF does. [125I]-EGF binding was inhibited by 50% by the peptide at 82.8 ng/ml and by unlabeled EGF at 71.4 ng/ml. This suggests that the growth stimulating effect of the peptide on 3T3 fibroblasts is mediated via the EGF receptor, and also suggests that the partial homologous sequence between monitor peptide and EGF is required for the receptor binding, or that the EGF receptor has a broad ligand specificity.

Amino Acid Sequence↗
PubMed1992

Chromogranin A epitopes: clues from synthetic peptides and peptide mapping.

Chromogranin A (CgA) is a 48 kDa acidic protein in neuroendocrine secretory vesicles whose primary structure is now known. We used synthetic peptides, synthetic peptide antisera, intact molecule antisera, chymotryptic peptide mapping, microsequencing, immunoblotting, and immunoprecipitation to probe the location of immunodominant domains within the CgA molecule. Polyclonal anti mid-molecule, anti N-terminal and anti C-terminal antibodies specifically visualized CgA (both bovine and human) in one and two dimensional immunoblots of adrenal chromaffin vesicles, and the stain CgA fragments further suggested bidirectional (both N- and C-terminal) cleavage or processing of CgA. Anti intact CgA immunoblotting of HPLC-separated peptides from chymotrypsin-digested bovine CgA revealed several strongly immunoreactive internal peptides, two of which were positioned by N-terminal amino acid sequencing: CgA91ff. and CgA197ff.. A single synthetic peptide (CgA79-113) was recognized by three antibodies developed against the intact CgA molecule: two polyclonal rabbit antisera as well as a monoclonal mouse antibody. Not all antigenicity algorithm-predicted domains were immunogenic, suggesting that some of these predicted domains may not be accessible. Polyclonal anti mid-molecule, anti N- and anti C-terminal synthetic peptide antisera specifically immunoprecipitated 125I-labeled bovine CgA from aqueous solution; mid-molecule antisera precipitated substantially greater amounts than terminal antisera. The immunoprecipitation results suggested exposed terminal as well as interior hydrophilic epitopes in the molecule in its intact, native conformation. 125I-human CgA was best precipitated by anti N-terminal antisera, consistent with greatest interspecies sequence conservation at the N-terminus of CgA. The terminal antisera reacted immunohistochemically in a granular pattern with adrenal medullary chromaffin cells (but not adrenal cortical cells) and pancreatic islet cells (but not pancreatic exocrine acini). Thus, synthetic and chymotryptic peptides yielded novel and specific insights into the structure, conformation, vesicular processing and interior immunodominant domains of CgA.

Amino Acid Sequence↗
PubMed1995

Low cerebrospinal fluid concentrations of peptide histidine valine and somatostatin-28 in Alzheimer's disease: altered processing of prepro-vasoactive intestinal peptide and prepro-somatostatin.

Recent studies have indicated that deposition of beta amyloid peptide in the brains of patients with senile dementia of the Alzheimer type (SDAT) is a consequence of abnormal processing of the beta amyloid protein precursor. In addition, reduced concentrations of various peptides have been measured in post-mortem brain tissue and cerebrospinal fluid (CSF) of patients with SDAT. We determined concentrations of the peptides derived from prepro-vasoactive intestinal peptide (VIP)--peptide histidine methionine-27 (PHM-27), peptide histidine valine (PHV) and VIP--and peptides derived from prepro-somatostatin (prepro-SS), SS-14 and SS-28, in CSF of patients with SDAT by radioimmunoassay combined with high performance liquid chromatography. We found significantly reduced levels of total PHM-immunoreactivity (IR) and PHV, and unaltered levels of PHM-27 and VIP in SDAT, compared with those in controls. Total SS-IR and SS-28 concentrations were significantly reduced in SDAT, while SS-14 levels did not differ from those of controls. These results suggest that an altered processing of the prepro-peptides of VIP and SS may occur in SDAT and that these alterations might have a significant role in the pathogenesis of SDAT.

Aged↗
PubMedDate not supplied

Effects of prepro-vasoactive intestinal peptide-derived peptides on the murine immune response.

We have studied the effects of prepro-vasoactive intestinal polypeptide-derived peptides on lectin-induced lymphocyte proliferation and natural killer cell (NK) activity in cells from murine spleen, mesenteric lymph nodes, Peyer's patches, thymus and peripheral blood mononuclear lymphocytes (PBL). These peptides (vasoactive intestinal peptide (VIP), peptide histidine methionine (PHM-27) and peptide histidine valine (PHV-42)) showed differential effects in their immune response in a dose- and tissue-dependent manner. All peptides significantly decreased DNA synthesis in spleen (range: 45-30%), lymph nodes (range: 30-0%), Peyer's patches (range: 30-4%) and PBL (range: 30-16%). In these tissues there was no significant difference in their potency. In the thymus, however, PHM-27 (range: 27-15%) was significantly more potent (p less than 0.001) in inhibiting DNA synthesis than either VIP (range: 6-0%) or PHV-42 (range: 20-8%). The modulatory effects on NK activity by these peptides also showed an inhibitory effect. The order of potency was: VIP (range: 40-27%), PHV-42 (range: 22-11%) and PHM-27 (range: 20-8%). The presence of VIP inhibitor [( D-p-chloro-Phe6,Leu17]-VIP) at 10(-8) M in both functional assays caused a significant antagonism of the effects of VIP but not PHM-27 or PHV-42. Our results suggest the existence on lymphocytes of different receptors for prepro-VIP-derived peptides, and that they may be considered as important immunoregulatory molecules. Their mechanism of interaction, however, is not clearly understood.

Animals↗
PubMed1996

The pregnant ovine endometrium constitutively expresses and secretes a highly stable bombesin-like peptide, which shares C-terminal sequence but differs structurally from gastrin-releasing peptide.

Previous studies have shown that a peptide closely related to gastrin releasing peptide (GRP) is expressed by the pregnant ovine endometrium throughout gestation, however its molecular form and the mode of its secretion have not been defined. We have partially purified the endometrial GRP-like peptide and characterised it chromatographically. In contrast to other tissues, the main molecular form of endometrial GRP is larger (6-8 kDa versus 1-3 kDa), and based on the increased hydrophobicity of its circulating form after reduction, contains at least one disulfide bond. Reduction and treatment with chaotropic agents showed that the protein is not a cleavage product of pro-GRP bound to a binding protein. Tryptic cleavage demonstrated that the C-terminus of the peptide is closely related to GRP18-27 suggesting that bioactivity is likely. The partially purified peptide remained intact after incubation in ovine plasma for 16 h indicating that it is extremely stable and consistent with an hormonal role during pregnancy. Quantification of peptide from monolayer cultures of ovine endometrial cells showed that the GRP-like peptide was secreted constitutively. These data show that a stable, GRP-like peptide, distinct from the known processing products of pre-pro-GRP is constitutively expressed by the gravid ovine endometrium. Since endometrial GRP has an intact bioactive C-terminus and is mitogenic for numerous tissues including the uterus, then it is likely to play an important regulatory role in ovine pregnancy.

Amino Acid Sequence↗
PubMed1995

B/PI-derived synthetic peptides: synergistic effects in tethered bactericidal and endotoxin neutralizing peptides.

Human neutrophil bactericidal protein (B/PI) is known for its ability to kill bacteria and to neutralize the action of endotoxin. Short linear peptides derived from residues 80-109 have been synthesized and their bactericidal and endotoxin neutralizing activities have been assayed. A series of 'walk-through' decapeptides, overlapping 3 to 4 residues, indicates that endotoxin neutralizing and partial bactericidal activities can be localized within the N- and C-terminal portions, respectively, of the 80-109 sequence. Bactericidal activity toward Pseudomonas aeruginosa was localized in central peptides of the walk-through series and greatest in peptide 90-99. By using longer peptides, residues 86-104 and 82-108, both bactericidal and endotoxin neutralizing activities are significantly enhanced. Bactericidal activity of peptide 82-108 is now only 6-fold less than that of parent B/PI and 9-fold more potent than peptide 86-104. The 82-108 peptide was 7-fold more active at endotoxin neutralization than 86-104 but showed less enhanced activity, being approx. 470-times less active than B/PI. Cyclized 82-108 peptide retained bactericidal activity but did not improve in capacity to neutralize endotoxin.

Amino Acid Sequence↗
PubMed2006

Peptides derived from HIV-1, HIV-2, Ebola virus, SARS coronavirus and coronavirus 229E exhibit high affinity binding to the formyl peptide receptor.

Peptides derived from the membrane proximal region of fusion proteins of human immunodeficiency viruses 1 and 2, Coronavirus 229 E, severe acute respiratory syndrome coronavirus and Ebola virus were all potent antagonists of the formyl peptide receptor expressed in Chinese hamster ovary cells. Binding of viral peptides was affected by the naturally occurring polymorphisms at residues 190 and 192, which are located at second extracellular loop-transmembrane helix 5 interface. Substitution of R190 with W190 enhanced the affinity for a severe acute respiratory syndrome coronavirus peptide 6 fold but reduced the affinity for N-formyl-Nle-Leu-Phe by 2.5 fold. A 12 mer peptide derived from coronavirus 229E (ETYIKPWWVWL) was the most potent antagonist of the formyl peptide receptor W190 with a K(i) of 230 nM. Fluorescently labeled ETYIKPWWVWL was effectively internalized by all three variants with EC(50) of approximately 25 nM. An HKU-1 coronavirus peptide, MYVKWPWYVWL, was a potent antagonist but N-formyl-MYVKWPWYVWL was a potent agonist. ETYIKPWWVWL did not stimulate GTPgammaS binding but inhibited the stimulation by formyl-NleLeuPhe. It also blocked beta arrestin translocation and receptor downregulation induced by formyl-Nle-Leu-Phe. This indicates that formyl peptide receptor may be important in viral infections and that variations in its sequence among individuals may affect their likelihood of viral and bacterial infections.

Amino Acid Sequence↗
PubMed2006

Peptide-lipid interactions of the beta-hairpin antimicrobial peptide tachyplesin and its linear derivatives from solid-state NMR.

The peptide-lipid interaction of a beta-hairpin antimicrobial peptide tachyplesin-1 (TP-1) and its linear derivatives are investigated to gain insight into the mechanism of antimicrobial activity. (31)P and (2)H NMR spectra of uniaxially aligned lipid bilayers of varying compositions and peptide concentrations are measured to determine the peptide-induced orientational disorder and the selectivity of membrane disruption by tachyplesin. The disulfide-linked TP-1 does not cause any disorder to the neutral POPC and POPC/cholesterol membranes but induces both micellization and random orientation distribution to the anionic POPE/POPG membranes above a peptide concentration of 2%. In comparison, the anionic POPC/POPG bilayer is completely unaffected by TP-1 binding, suggesting that TP-1 induces negative curvature strain to the membrane as a mechanism of its action. Removal of the disulfide bonds by substitution of Cys residues with Tyr and Ala abolishes the micellization of POPE/POPG bilayers but retains the orientation randomization of both POPC/POPG and POPE/POPG bilayers. Thus, linear tachyplesin derivatives have membrane disruptive abilities but use different mechanisms from the wild-type peptide. The different lipid-peptide interactions between TP-1 and other beta-hairpin antimicrobial peptides are discussed in terms of their molecular structure.

Antimicrobial Cationic Peptides↗
PubMed2005

Dietary lactitol fermentation increases circulating peptide YY and glucagon-like peptide-1 in rats and humans.

OBJECTIVE: Recently peptide YY (PYY) has attracted interest as a possible regulator of food intake. Release of PYY by nutrients in the distal small intestine is thought to contribute to the so-called ileal brake by inhibiting motility and secretion in the foregut. Our objective was to establish whether plasma concentrations of the gut peptides PYY and glucagon-like peptide-1 in rats and humans change in response to intake of a non-absorbable but fermentable carbohydrate. METHODS: The acute response was determined in rats by killing animals 0, 5, 10, and 24 h after a single meal with or without lactitol (100 g/kg of semisynthetic diet) and measuring PYY and glucan-like peptide-1 concentrations in plasma. Food intake, body mass, and plasma peptide levels were also determined in rats fed the same diet for 10 d. Healthy human volunteers consumed lactitol or sucrose as a fruit-flavored drink. Breath hydrogen levels were measured at 45-min intervals over the next 7.5 h and plasma peptide concentrations were assessed after 0 and 5 h. Volunteers were also asked to complete a questionnaire to record satiety and well-being. RESULTS: Ingestion of lactitol significantly increased the acute postprandial PYY response in rats, and prolonged consumption decreased weight gain in growing rats. In humans given a single dose of lactitol, the effects on PYY were much less marked but the postprandial decrease in circulating concentrations of PYY was attenuated. There was no effect on plasma glucan-like peptide-1. CONCLUSION: Our observations are consistent with a role for fermentation products in the release of gastrointestinal peptides in the rat and, to a lesser extent, in humans.

Analysis of Variance↗
PubMed2002

Design of novel peptide analogs with potent fungicidal activity, based on PMAP-23 antimicrobial peptide isolated from porcine myeloid.

PMAP-23 is a 23-mer peptide derived from porcine myeloid. To develop novel antifungal peptides useful as therapeutic drugs, it would require a strong fungicidal activity against pathogenic fungal cells. To this goal, several analogs, with amino acid substitutions, were designed to increase the net hydrophobicity by Trp (W)-substitution at positions 10, 13, or 14 at the hydrophilic face of PMAP-23 without changing the hydrophobic helical face. The Trp (W)-substitution (P6) showed an enhanced fungicidal and antitumor activities, with the fungicidal activity inhibited by salts and the respiratory inhibitor, NaN(3). The results suggested that the increase of hydrophobicity of the peptides correlated with fungicidal activity. The fungicidal effects of analog peptides were further investigated using 1,6-diphenyl-1,3,5-hexatriene (DPH) as a membrane probe. In Candida albicans, the analog peptide (P6) exerted its fungicidal effect on the blastoconidia in 20% fetal bovine serum by disrupting the mycelial forms. Furthermore, P6 caused significant morphological changes, and these facts suggested that the fungicidal function of the novel analog peptide (P6) was by damaging the fungal cell membranes. Thus, this peptide may provide a useful template for designing novel antifungal peptides useful for the treatment of infectious diseases.

Amino Acid Sequence↗