Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “PEPTIDES”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 271 records · Page 15Linked to original sources
PubMed1990

Experimental evidence for predicted transmembrane peptide topography: incorporation of hydrophobic peptide alpha-helical rods with an N-terminal positive charge having a length comparable to the thickness of lipid bilayers into the membranes.

Liposomes consisting of egg yolk phosphatidylcholine and hydrophobic peptides Nps- and Cl-.+H2-(Met-Met-Leu)n-OEt (n = 6-10) with various polypeptide chain lengths were prepared by the sonication method. The conformation of the peptides incorporated into the liposomes was examined by CD spectroscopy. All the peptides incorporated assumed alpha-helical conformation. Quantitative analyses of the peptides and lipids in the membranes showed that the concentration of the peptides with a positive charge at the N-terminus in the liposomes decreased markedly as the peptide chain length increased, reaching zero for the peptides over n = 8. The peptides without a positive charge were hardly incorporated into the liposomes. Infrared attenuated reflection spectroscopy of multilayered membranes containing the peptides suggests that the axis of the alpha-helical peptide rods is oriented in parallel with the molecular axis of lipids in the membranes. These results suggest that the hydrophobic peptides can be incorporated into the lipid bilayers of the liposomes in the alpha-helical conformation, the rods of which have a length comparable to the thickness of the lipid bilayers, and the N-terminal positive charge of the peptides is essential for the stable peptide incorporated into the membranes.

Amino Acid Sequence↗
PubMed1996

Multiple HLA-A alleles can present an immunodominant peptide of the human melanoma antigen Melan-A/MART-1 to a peptide-specific HLA-A*0201+ cytotoxic T cell line.

The majority of HLA-A*0201-restricted tumor-infiltrating lymphocytes from melanoma patients recognize a peptide, MT(27-35), derived from the Melan-A/MART-1 Ag. This study reports that six variants of HLA-A2 and the HLA-A28 subtype A*6901 can present peptide MT(27-35). A CTL line specific for peptide MT(27-35) was generated by in vitro stimulation of PBL of an HLA-A*0201+, healthy donor with peptide-pulsed, activated autologous B lymphoblasts. This CTL line was shown to recognize peptide MT(27-35) after endogenous processing on Melan-A/MART-1+/HLA-A2+ tumor cells. Moreover, a panel of B lymphoblastoid cell lines (BLCLs) expressing A*0202, A*0204, A*0205, A*0206, A*0209, and with lower efficiency A*6901, could be sensitized to lysis upon incubation with the relevant peptide. As demonstrated by the levels of ED50 and CD8 dependency of lysis, HLA-A*0204 and HLA-A*0205 presented the peptide as efficiently as HLA-A*0201, while the other four alleles were less efficient. Peptide-binding studies suggest that TCR- rather than peptide-binding affinity determines the T cell recognition levels of peptide-pulsed EBV-BLCLs expressing A*0201, A*0204, A*0206, and A*0209. Peptide-pulsed BLCLs expressing HLA-A*0207 or two additional subtypes of HLA-A28 were not recognized. MT(27-35)-specific CTL could also be raised from donors expressing HLA-A*0205. These findings have implications on the applicability of peptide vaccination with peptide MT(27-35) on melanoma patients.

Alleles↗
PubMed2000

Reactivity of natural and induced human antibodies to MUC1 mucin with MUC1 peptides and n-acetylgalactosamine (GalNAc) peptides.

Antibodies (Abs) to MUC1 occur naturally in both healthy subjects and cancer patients and can be induced by MUC1 peptide vaccination. We compared the specificity of natural and induced MUC1 Abs with the objective of defining an effective MUC1 vaccine for active immunotherapy of adenocarcinoma patients. Serum samples, selected out of a screened population of 492 subjects for their high levels of IgG and/or IgM MUC1 Abs, were obtained from 55 control subjects and from 26 breast cancer patients before primary treatment, as well as from 19 breast cancer patients immunized with MUC1 peptides coupled to keyhole limpet hemocyanin (KLH) and mixed with QS-21. The samples were tested with enzyme-linked immunoassays for reactivity with (1) overlapping hepta- and 20-mer peptides spanning the MUC1 tandem repeat sequence; (2) two modified 60-mer peptides with substitutions in the PDTR (PDTA) or in the STAPPA (STAAAA) sequence of each tandem repeat; and (3) four 60-mer glycopeptides with each 1, 2, 3 and 5 mol N-acetylgalactosamine (GalNAc) per repeat. More than one minimal epitopic sequence could be defined, indicating that Abs directed to more than one region of the MUC1 peptide core can coexist in one and the same subject. The most frequent minimal epitopic sequence of natural MUC1 IgG and IgM Abs was RPAPGS, followed by PPAHGVT and PDTRP. MUC1 peptide vaccination induced high titers of IgM and IgG Abs predominantly directed, respectively, to the PDTRPAP and the STAPPAHGV sequences of the tandem repeat. Natural MUC1 Abs from breast cancer patients reacted more strongly with the N-acetylgalactosamine (GalNAc) peptides than with the naked 60-mer peptide, while reactivity with the GalNAc-peptides was significantly reduced (2-tailed p < 0.0001) in the MUC1 IgG and IgM Abs induced by MUC1 peptide vaccination. Whereas in cancer patients glycans appear to participate in epitope conformation, the epitope(s) recognized by MUC1 Abs induced by peptide vaccination are already masked by minimal glycosylation. Therefore, our results indicate that a MUC1 glycopeptide would be a better vaccine than a naked peptide.

Acetylgalactosamine↗
PubMed2002

Molecular complementarity III. peptide complementarity as a basis for peptide receptor evolution: a bioinformatic case study of insulin, glucagon and gastrin.

Dwyer has suggested that peptide receptors evolved from self-aggregating peptides so that peptide receptors should incorporate regions of high homology with the peptide ligand. If one considers self-aggregation to be a particular manifestation of molecular complementarity in general, then it is possible to extend Dwyer's hypothesis to a broader set of peptides: complementary peptides that bind to each other. In the latter case, one would expect to find homologous copies of the complementary peptide in the receptor. Thirteen peptides, 10 of which are not known to self-aggregate (amylin, ACTH, LHRH, angiotensin II, atrial natriuretic peptide, somatostatin, oxytocin, neurotensin, vasopressin, and substance P), and three that are known to self-aggregate (insulin, glucagon, and gastrin), were chosen. In addition to being self-aggregating, insulin and glucagon are also known to bind to each other, making them a mutually complementary pair. All possible combinations of the 13 peptides and the extracellular regions of their receptors were investigated using bioinformatic tools (a total of 325 combinations). Multiple, statistically significant homologies were found for insulin in the insulin receptor; insulin in the glucagon receptor; glucagon in the glucagon receptor; glucagon in the insulin receptor; and gastrin in gastrin binding protein and its receptor. Most of these homologies are in regions or sequences known to contribute to receptor binding of the respective hormone. These results suggest that the Dwyer hypothesis for receptor evolution may be generalizable beyond self-aggregating to complementary peptides. The evolution of receptors may have been driven by small molecule complementarity augmented by modular evolutionary processes that left a "molecular paleontology" that is still evident in the genome today. This "paleontology" may allow identification of peptide receptor sites.

Computational Biology↗
PubMed2003

Improvement of biological activity and proteolytic stability of peptides by coupling with a cyclic peptide.

The cyclic moiety of an endothelin antagonist peptide RES-701-1, composed of 10 amino acids with an amide bond between alpha-NH(2) of Gly1 and beta-COOH of Asp9, was coupled to some biologically active peptides aiming to improve their activities and stabilities against proteolytic degradation. Coupling of the cyclic peptide to the N-terminal of RGD-peptides, maximally 4-fold improvement of in vitro activity compared to the original peptide has been achieved. Coupling of it to protein farnesyltransferase inhibiting peptides resulted to improve in vitro activity maximally 3-fold. These peptides coupled with the cyclic peptide also showed enhanced stability against some typical proteases. These results indicate that this cyclic peptide can stabilize the conformations of the peptides coupled to its C-terminus. Coupling of our cyclic peptide is anticipated to be a novel conformational stabilizing method for biologically active peptides, results to improve their activity and stability.

Alkyl and Aryl Transferases↗
PubMed2002

The thioesterase domain from a nonribosomal peptide synthetase as a cyclization catalyst for integrin binding peptides.

Nonribosomal peptide synthetases responsible for the production of macrocyclic compounds often use their C-terminal thioesterase (TE) domain for enzymatic cyclization of a linear precursor. The excised TE domain from the nonribosomal peptide synthetase responsible for the production of the cyclic decapeptide tyrocidine A, TycC TE, retains autonomous ability to catalyze head-to-tail macrocyclization of a linear peptide thioester with the native sequence of tyrocidine A and can additionally cyclize peptide analogs that incorporate limited alterations in the peptide sequence. Here we show that TycC TE can catalyze macrocyclization of peptide substrates that are dramatically different from the native tyrocidine linear precursor. Several peptide thioesters that retain a limited number of elements of the native peptide sequence are shown to be substrates for TycC TE. These peptides were designed to integrate an Arg-Gly-Asp sequence that confers potential activity in the inhibition of ligand binding by integrin receptors. Although enzymatic hydrolysis of the peptide thioester substrates is preferred over cyclization, TycC TE can be used on a preparative scale to generate both linear and cyclic peptide products for functional characterization. The products are shown to be inhibitors of ligand binding by integrin receptors, with cyclization and N(alpha)-methylation being important contributors to the nanomolar potency of the best inhibitors of fibrinogen binding to alpha IIb beta 3 integrin. This study provides evidence for TycC TE as a versatile macrocyclization catalyst and raises the prospect of using TE catalysis for the generation of diverse macrocyclic peptide libraries that can be probed for novel biological function.

Amino Acid Sequence↗
PubMed2002

Cell-dependent differential cellular uptake of PNA, peptides, and PNA-peptide conjugates.

Peptide nucleic acid (PNA) oligomers were conjugated to cell-penetrating peptides: pAnt, a 17-residue fragment of the Drosophila protein Antennapedia, and pTat, a 14-amino acid fragment of HIV protein Tat. A 14-mer PNA was attached to the peptide by disulfide linkage or by maleimide coupling. The uptake of (directly or indirectly, via biotin) fluorescein-labeled peptides, PNAs, or PNA-peptide conjugates was studied by fluorescence microscopy, confocal laser scanning microscopy, and fluorometry in five cell types. In SK-BR-3, HeLa, and IMR-90 cells, the PNA-peptide conjugates and a T1, backbone-modified PNA were readily taken up (2 microM). The PNA was almost exclusively confined to vesicular compartments in the cytosol. However, the IMR-90 cells also showed a weak diffuse staining of the cytoplasm. In the U937 cells, we observed a very weak and exclusively vesicular staining with the PNA-peptide conjugates and the T(lys)-modified PNA. No evident uptake of the unmodified PNA was seen. In H9 cells, both peptides and the PNA-peptide conjugates quickly associated with the membrane, followed by a weak intracellular staining. A cytotoxic effect resulting in artificial staining of the cells was observed with fluoresceinated peptides and PNA-peptide conjugates at concentrations above 5-10 microM, depending on cell type and incubation time. We conclude that uptake of PNAs in many cell types can be achieved either by conjugating to certain peptides or simply by charging the PNA backbone using lysine PNA units. The uptake is time, temperature, and concentration dependent and mainly endocytotic. Our results also show that proper controls for cytotoxicity should always be carried out to avoid misinterpretation of visual data.

Amino Acid Sequence↗
PubMed1998

The path of the growing peptide chain through the 23S rRNA in the 50S ribosomal subunit; a comparative cross-linking study with three different peptide families.

As part of a programme to investigate the path of the nascent peptide through the large ribosomal subunit, peptides of different lengths (up to 30 amino acids), corresponding to the signal peptide sequence and N-terminal region of the Escherichia coli ompA protein, were synthesized in situ on E.coli ribosomes. The peptides each carried a diazirine moiety attached to their N-terminus which, after peptide synthesis, was photoactivated so as to induce cross-links to the 23S rRNA. The results showed that, with increasing length, the peptides became progressively cross-linked to sites in Domains V, II, III and I of the 23S rRNA, in a similar manner to that previously observed with a family of peptides derived from the tetracycline resistance gene. However, the cross-links to Domain III appeared at a shorter peptide length (12 aa) in the case of the ompA sequence, and an additional cross-link in Domain II (localized to nt 780-835) was also observed from this peptide. As with the tetracycline resistance sequence, peptides of all lengths were still able to form cross-links from their N-termini to the peptidyl transferase centre in Domain V. A further set of peptides (30 or 50 aa long), derived from mutants of the bacteriophage T4 gene 60 sequence, did not show the cross-links to Domain III, but their N-termini were nevertheless cross-linked to Domain I and to the sites in Domains II and V. The ability of relatively long peptides to fold back towards the peptidyl transferase centre thus appears to be a general phenomenon.

Amino Acid Sequence↗
PubMed1984

[A study on salivary peptide P-C with special reference to intracellular localization of salivary peptide P-C like immunoreactivity in the human pancreatic B-cells].

In order to clarify the intracellular localization of salivary peptide P-C like immunoreactivity in the human pancreatic B-cells, an immuno-electronmicroscopical study using protein A-gold technique was carried out on the human foetal pancreas. Salivary peptide P-C like immunoreactivity was present in some of insulin secretory granules while insulin like immunoreactivity was found in all insulin secretory granules. The finding suggested that new substance in addition to insulin and its precursor was present in the insulin secretory granules of the human pancreatic B-cells. Furthermore, the finding seemed to explain the previous study that development of salivary peptide'P-C like immunoreactivity in the foetal pancreatic B-cells was immature in compared to that in the human adult pancreatic B-cells. In addition, to examine whether or not, salivary peptide P-C like immunoreactivity in the human pancreatic B-cells is Salivary Protein C, an indirect immunofluorescence technique using three kinds of antisera against salivary peptide P-C, Salivary Protein C and salivary peptide P-B, and using their antigens was undertaken on the adult pancrease. From the results of the study, it was thought that salivary peptide P-C like immunoreactivity in the human pancreas was neither Salivary Protein C itself, nor salivary peptide P-B itself, but was either salivary peptide P-C itself or unknown substance which had the common antigenic determinant with salivary peptide P-C, P-B and Salivary Protein C, since salivary peptide P-C like immunoreactivity in the human pancreas disappeared in the sections in which P-C antisera preincubated with each of salivary peptide P-C, P-B and Salivary Protein C were used as the primary antisera. Thus, although new substance was present in the insulin secretory granules of the human pancreatic B-cells, its pathophysiological role remained to be elucidated.

Cytoplasmic Granules↗
PubMed1993

Cloned T cells internalize peptide from bound complexes of peptide and purified class II major histocompatibility complex antigen.

Antigen presentation to helper T cells involves the formation of a trimolecular complex consisting of a class II major histocompatibility complex (MHC) antigen combined with an antigenic peptide on the surface of an antigen-presenting cell and a T cell receptor (TCR) on the T cell. The fate of the MHC class II, peptide, or TCR moieties of the ternary complex following antigen presentation is unknown. Using radiolabeled complexes of affinity-purified murine MHC class II molecules and peptides corresponding to T cell epitopes of myelin basic protein (MBP), this report presents evidence that the binding of preformed relevant MHC class II-peptide complexes to cloned T cells in vitro results in internalization of the peptide moiety. Neither the restricting MHC class II molecule nor the TCR moiety of the trimolecular complex was internalized by T cells. The specificity of peptide internalization was demonstrated using complexes of syngeneic MHC class II with an irrelevant MBP peptide analog and by cloned T cells restricted for a different epitope of the same MBP antigen. Furthermore, the peptide translocation mediated by MHC class II and TCR was demonstrated by antibody-blocking experiments using anti-class and anti-TCR monoclonal antibodies. The peptide internalization by T cells was markedly reduced when binding was performed at 4 degrees C as compared with 37 degrees C. In addition, a significant inhibition of peptide translocation was observed in the presence of a metabolic inhibitor (sodium azide) but not in the presence of cytochalasin B. These results together demonstrate that the in vitro interaction of soluble MHC II-peptide complexes with cloned T cells is an active process associated with uptake of the antigenic peptide.

Amino Acid Sequence↗
PubMed1993

Dipeptidyl-peptidase IV hydrolyses gastric inhibitory polypeptide, glucagon-like peptide-1(7-36)amide, peptide histidine methionine and is responsible for their degradation in human serum.

Peptides of the glucagon/vasoactive-intestinal-peptide (VIP) peptide family share a considerable sequence similarity at their N-terminus. They either start with Tyr-Ala, His-Ala or His-Ser which might be in part potential targets for dipeptidyl-peptidase IV, a highly specialized aminopeptidase removing dipeptides only from peptides with N-terminal penultimate proline or alanine. Growth-hormone-releasing factor (1-29)amide and gastric inhibitory peptide/glucose-dependent insulinotropic peptide (GIP) with terminal Tyr-Ala as well as glucagon-like peptide-1(7-36)amide/insulinotropin [GLP-1(7-36)amide] and peptide histidine methionine (PHM) with terminal His-Ala were hydrolysed to their des-Xaa-Ala derivatives by dipeptidyl-peptidase IV purified from human placenta. VIP with terminal His-Ser was not significantly degraded by the peptidase. The kinetics of the hydrolysis of GIP, GLP-1(7-36)amide and PHM were analyzed in detail. For these peptides Km values of 4-34 microM and Vmax values of 0.6-3.8 mumol.min-1.mg protein-1 were determined for the purified peptidase which should allow their enzymic degradation also at physiological, nanomolar concentrations. When human serum was incubated with GIP or GLP-1(7-36)amide the same fragments as with the purified dipeptidyl-peptidase IV, namely the des-Xaa-Ala peptides and Tyr-Ala in the case of GIP or His-Ala in the case of GLP-1(7-36)amide, were identified as the main degradation products of these peptide hormones. Incorporation of inhibitors specific for dipeptidyl-peptidase IV, 1 mM Lys-pyrrolidide or 0.1 mM diprotin A (Ile-Pro-Ile), completely abolished the production of these fragments by serum. It is concluded that dipeptidyl-peptidase IV initiates the metabolism of GIP and GLP-1(7-36)amide in human serum. Since an intact N-terminus is obligate for the biological activity of the members of the glucagon/VIP peptide family [e. g. GIP(3-42) is known to be inactive to release insulin in the presence of glucose as does intact GIP], dipeptidyl-peptidase-IV action inactivates these peptide hormones. The relevance of this finding for their inactivation and their determination by immunoassays is discussed.

Amino Acid Sequence↗