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At least 595 records · Page 33Linked to original sources
PubMed2006

Synthesis of the aglycone of the shark repellent pavoninin-4 using remote functionalization.

[reaction: see text] The aglycone of shark repellent pavoninin-4, (25R)-5alpha-cholestan-3alpha,15alpha,26-triol 26-acetate 1a, was synthesized from (25R)-cholest-5-en-3beta,26-diol 4 (26-hydroxycholesterol) in eight steps in 18% overall yield. Breslow's remote functionalization strategy was used as a key step to introduce the C-15alpha alcohol on a steroid D ring. An efficient synthesis of the 26-hydroxycholesterol from the 16beta hydroxyl steroid, (25R)-cholest-5-ene-3beta,16beta,26-triol (3a), is also reported.

Aminoglycosides↗
PubMed1997

Diets enriched in menhaden fish oil, seal oil, or shark liver oil have distinct effects on the lipid and fatty-acid composition of guinea pig heart.

The purpose of this investigation was to determine whether diets supplemented with oils from three different marine sources, all of which contain high proportions of long-chain n-3 polyunsaturated fatty acids (PUFA), result in qualitatively distinct lipid and fatty acid profiles in guinea pig heart. Albino guinea pigs (14 days old) were fed standard, nonpurified guinea pig diets (NP) or NP supplemented with menhaden fish oil (MO), harp seal oil (SLO) or porbeagle shark liver oil (PLO) (10%, w/w) for 4-5 weeks. An n-6 PUFA control group was fed NP supplemented with corn oil (CO). All animals appeared healthy, with weight gains marginally lower in animals fed the marine oils. Comparison of relative organ weights indicated that only the livers responded to the diets, and that they were heavier only in the marine-oil fed guinea pigs. Heart total cholesterol levels were unaffected by supplementing NP with any of the oils, whereas all increased the triacylglycerol (TAG) content. The fatty-acid profiles of total phospholipid (TPL), TAG and free fatty acid (FFA) fractions of heart lipids showed that feeding n-3 PUFA significantly altered the proportions of specific fatty-acid classes. For example, all marine-oil-rich diets were associated with increases in total monounsaturated fatty acids in TPL (p < 0.05), and with decreases in total saturates in TAG (p < 0.05). Predictably, the n-3 PUFA enriched regimens significantly increased the cardiac content of n-3 PUFA and decreased that of n-6 PUFA, although the extent varied among the diets. As a result, n-6/n-3 ratios were significantly lower in all myocardial lipid classes of marine-oil-fed guinea pigs. Analyses of the profiles of individual PUFA indicated that quantitatively, the fatty acids of the three marine oils were metabolized and/or incorporated into TPL, TAG and FFA in a diet-specific manner. In animals fed MO-enriched diets in which eicosapentaenoic acid (EPA) > docosahexacnoic acid (DHA), ratios of DHA/EPA in the hearts were 1.2, 2.2 and 1.5 in TPL, TAG and FFA, respectively. In SLO-fed guinea pigs in which dietary EPA approximately DHA, ratios of DHA/EPA were 0.9, 3.4 and 2.1 in TPL, TAG and FFA, respectively. Feeding NP + PLO (DHA/EPA = 4.8), resulted in values for DHA/EPA in cardiac tissue of 2.1, 10.6 and 2.9 in TPL, TAG and FFA, respectively. In the TAG and FFA, proportions of n-3 docosapentaenoic acid (n-3 DPA) were equal to or higher than EPA in the SLO- and PLO-fed animals. The latter group exhibited the greatest difference between the DHA/n-3 DPA ratio in the diet and in cardiac TAG and FFA fractions (7, 3.4 and 3.1, respectively). Quantitative analysis indicated that > or = 85% of the n-3 PUFA were in TPL, 7-11% were in TAG, and 2-6% were FFA. Specific patterns of distribution of EPA, DPA and DHA depended on the dietary oil. Both the qualitative and quantitative results of this study demonstrated that in guinea pigs, n-3 PUFA in different marine oils are metabolized and/or incorporated into cardiac lipids in distinct manners. In support of the concept that the diet-induced alterations reflect changes specifically in cardiomyocytes, we observed that direct supplementation of cultured guinea pig myocytes for 2-3 weeks with EPA or DHA produced changes in the PUFA profiles of their TPL that were qualitatively similar to those observed in tissue from the dietary study. The factors that regulate specific deposition of n-3 PUFA from either dietary oils or individual PUFA are not yet known, however the differences that we observed could in some manner be related to cardiac function and thus their relative potentials as health-promoting dietary fats.

Animals↗
PubMed2001

Resurrection of Perissopus galeorhini (Yamaguti, 1936), with notes on the genus Perissopus Steenstrup & Lütken, 1861 (Copepoda: Pandaridae) parasitic on sharks.

Recently collected copepod parasites on the narrownose smooth-hound shark Mustelus schmitti Springer revealed enough similarities with Perissopus galeorhini (Yamaguti, 1936) to be considered conspecific. Comparison of these specimens with the types of P. oblongus (Wilson, 1908) showed that P. galeorhini and P. oblongus are distinct species. Therefore, P. galeorhini is considered a valid species rather than a synonym of P. oblongus, as it has been treated since the revision of Cressey (1967). Descriptions of P. galeorhini from M. schmitti and type-material of P. oblongus are provided along with a discussion on their taxonomic status. P. galeorhini differs from P. oblongus in features relating to the anterior margin of cephalothorax, the dorsal plates of the third pedigerous segment and details of the segmentation and armature of the appendages. In addition, an amended diagnosis of Perissopus Steenstrup & and Lütken, 1861 is given, including characters not previously considered by Cressey (1967) such as: the dorsal plate of segment 2 can be small, widely separated, covered by the posterior end of the lateral processes of the cephalothorax and not always extending to the posterior border of the plates of segment 3; and the rami of legs 3 can be 2-segmented.

Animals↗
PubMed2000

Shark cartilage extracts as antiangiogenic agents: smart drinks or bitter pills?

The use of crude cartilage for the treatment of human cancers remains a subject of controversy. In this brief commentary, we reviewed the current knowledge on the anticancer properties of cartilage. We then presented the properties of AE-941, a novel standardized water-soluble extract derived from shark cartilage that represents less than 5% of the crude cartilage. It is a multifunctional antiangiogenic product that contains several biologically active molecules. EA-941 is one of the few antiangiogenic drugs that is under phase III clinical investigation. It is currently evaluated in Europe and North America for the treatment of refractory renal cell carcinoma and in North America for metastatic non small cell lung cancer.

Angiogenesis Inhibitors↗
PubMed1980

Lack of heterogeneity in antihapten antibodies of a phylogenetically primitive shark.

Individual mammals have the capacity to express at least one million distinct antigen binding specificities, implying a high degree of structural heterogeneity in the variable heavy and light chain (VH and VL) portions of the antibody molecules. Studies of higher vertebrate species suggest that this heterogeneity is created both through a sizeable repertoire of germ-line VH and VL genes and through random rearrangements of V and joining genes. Additional somatic mechanisms probably also contribute to the ultimate heterogeneity; one-third of murine plasmacytomas producing lambda 1 immunoglobulin carry a somatically mutated Ig1-V gene. The relative contributions of these various mechanisms to the overall imunoglobulin variability are difficult to evaluate. The production of different antibodies to a defined determinant in different individuals of an inbred mouse strain [for example, (3-iodo-4-hydroxy-5-nitrophenyl) acetyl (NIP) in CBA mice] suggests the involvement of somatic mutations or rearrangement but does not rule out the possibility that each individual CBA mouse expresses only a small random fraction from a large germ-line repertoire of V genes determining different anti-NIP binding sites. The opposite finding, that different individuals produce nearly identical antibodies to a defined determinant, would suggest the presence and expression of a limited number of germ-line genes without somatic alterations. Data presented here suggest that primitive sharks (Heterodontus fransisci) produce such antibodies to the hapten furyloxazolone.

Animals↗
PubMed1995

A new antigen receptor gene family that undergoes rearrangement and extensive somatic diversification in sharks.

Immunoglobulin and T-cell receptor (TCR) molecules are central to the adaptive immune system. Sequence conservation, similarities in domain structure, and usage of similar recombination signal sequences and recombination machinery indicate that there was probably a time during evolution when an ancestral receptor diverged to the modern-day immunoglobulin and TCR. Other molecules that undergo rearrangement have not been described in vertebrates, nor have intermediates been identified that have features of both these gene families. We report here the isolation of a new member of the immunoglobulin superfamily from the nurse shark, Ginglymostoma cirratum, which contains one variable and five constant domains and is found as a dimer in serum.

Amino Acid Sequence↗
PubMed1986

High-field n.m.r. studies of keratan sulphates. 1H and 13C assignments of keratan sulphate from shark cartilage.

Keratan sulphate was extracted from a shark/whale cartilage preparation and examined by 400 MHz 1H- and 100 MHz 13C-n.m.r. spectroscopy. Assignment of the majority of the resonances was facilitated by two-dimensional 13C-1H correlation by using a modified COLOC procedure and a COSY-45 experiment. The spectra are consistent with an N-acetyl-lactosamine repeating unit that is predominantly sulphated at C-6 of both galactose and N-acetylglucosamine. Gel chromatography of a keratanase digest of the shark keratan sulphate confirmed the high degree of galactose sulphation.

Animals↗
PubMed1999

The main fatty acid-binding protein in the liver of the shark (Halaetunus bivius) belongs to the liver basic type. Isolation, amino acid sequence determination and characterization.

Three fatty acid-binding proteins (FABPs) from the liver of the shark Halaetunus bivius were isolated and characterized: one of them belongs to the liver-type FABP family and the other two to the heart-type FABP family. The complete primary structure of the first FABP, and partial primary structures of the two others, were determined. The liver-type FABP constitutes 69% of the total FABPs, and its amino acid sequence presents the highest identity with chicken, catfish, iguana and elephant fish liver basic FABPs. The L-FABP protein has low affinity for palmitic and oleic acids and high affinity for linoleic and arachidonic acids and other hydrophobic ligands, all of them important for the metabolic functions of the liver. In contrast, both heart-type FABPs have the highest affinity for palmitic acid, the principal fatty acid mobilized from fat deposits for beta-oxidation.

Amino Acid Sequence↗
PubMed2004

Structural evidence for evolution of shark Ig new antigen receptor variable domain antibodies from a cell-surface receptor.

The Ig new antigen receptors (IgNARs) are single-domain antibodies found in the serum of sharks. Here, we report 2.2- and 2.8-A structures of the type 2 IgNAR variable domains 12Y-1 and 12Y-2. Structural features include, first, an Ig superfamily topology transitional between cell adhesion molecules, antibodies, and T cell receptors; and, second, a vestigial complementarity-determining region 2 at the "bottom" of the molecule, apparently discontinuous from the antigen-binding paratope and similar to that observed in cell adhesion molecules. Thus, we suggest that IgNARs originated as cell-surface adhesion molecules coopted to the immune repertoire and represent an evolutionary lineage independent of variable heavy chain/variable light chain type antibodies. Additionally, both 12Y-1 and 12Y-2 form unique crystallographic dimers, predominantly mediated by main-chain framework interactions, which represent a possible model for primordial cell-based interactions. Unusually, the 12Y-2 complementarity-determining region 3 also adopts an extended beta-hairpin structure, suggesting a distinct selective advantage in accessing cryptic antigenic epitopes.

Animals↗
PubMed1985

Immunoglobulin VH gene structure and diversity in Heterodontus, a phylogenetically primitive shark.

A mouse VH probe has been used to identify and isolate VH homologs in a DNA library of Heterodontus francisci (horned shark). The complete nucleotide sequence of one VH gene, HXIA, has been determined and found to exhibit striking organizational homology and nucleotide identity with mammalian prototype VH genes. Metric analysis of the complete sequence is consistent with the early phylogenetic diversification of framework and complementarity-determining regions (CDR). Both the predicted amino acid sequence and the specific hybridization of the CDR2-specific, synthetic oligodeoxynucleotide probe in spleen mRNA suggest that HXIA is functionally expressed. A probe consisting of the entire coding region of this gene hybridizes with multiple components in Southern blot analysis of Heterodontus genomic DNA and together with the identification of additional unique VH+-lambda clones indicates that considerable complexity is associated with the germline VH gene family in a contemporary species that represents an early stage in the phylogenetic development of the vertebrates.

Amino Acid Sequence↗
PubMed2001

Bimodal regulation of Na(+)--Ca(2+) exchanger by beta-adrenergic signaling pathway in shark ventricular myocytes.

In shark heart, the Na(+)--Ca(2+) exchanger serves as a major pathway for both Ca(2+) influx and efflux, as there is only rudimentary sarcoplasmic reticulum in these hearts. The modulation of the exchanger by a beta-adrenergic agonist in whole-cell clamped ventricular myocytes was compared with that of the Na(+)--Ca(2+) exchanger blocker KB-R7943. Application of 5 microM isoproterenol and 10 microM KB-R7943 suppressed both the inward and the outward Na(+)--Ca(2+) exchanger current (I(Na--Ca)). The isoproterenol effect was mimicked by 10 microM forskolin. Isoproterenol and forskolin shifted the reversal potential (E(rev)) of I(Na--Ca) by approximately -23 mV and -30 mV, respectively. An equivalent suppression of outward I(Na--Ca) by KB-R7943 to that by isoproterenol produced a significantly smaller shift in E(rev) of about --4 mV. The ratio of inward to outward exchanger currents was also significantly larger in isoproterenol- than in control- and KB-R7943-treated myocytes. Our data suggest that the larger ratio of inward to outward exchanger currents as well as the larger shift in E(rev) with isoproterenol results from the enhanced efficacy of Ca(2+) efflux via the exchanger. The protein kinase A-mediated bimodal regulation of the exchanger in parallel with phosphorylation of the Ca(2+) channel and enhancement of its current may have evolved to satisfy the evolutionary needs for accelerated contraction and relaxation in hearts of animals with vestigial sarcoplasmic Ca(2+) release stores.

Adrenergic beta-Agonists↗
PubMed2004

Novel 70-kDa chondroitin sulfate/dermatan sulfate hybrid chains with a unique heterogeneous sulfation pattern from shark skin, which exhibit neuritogenic activity and binding activities for growth factors and neurotrophic factors.

Chondroitin sulfate (CS) and dermatan sulfate (DS) hybrid chains of proteoglycans are critical in growth factor binding, neuritogenesis, and brain development. Here we isolated CS/DS hybrid chains from shark skin aiming to develop therapeutic agents. Digestion with various chondroitinases showed that both GlcUA- and IdoUA-containing disaccharides are scattered along the polysaccharide chains with an unusually large average molecular mass of 70 kDa. The CS/DS chains were separated into major (80%) and minor (20%) fractions by anion-exchange chromatography. Both fractions had relatively low degrees of sulfation (sulfate/disaccharide molar ratio=1.17 versus 0.87), showing a unique feature compared with the marine CS and DS isolated to date, most of which are oversulfated. They were highly heterogeneous and characterized by multiple disaccharides including GlcUA-GalNAc, GlcUA-GalNAc(6S), GlcUA-GalNAc(4S), IdoUA-GalNAc(4S), GlcUA-GalNAc(4S,6S), IdoUA-GalNAc(4S,6S), GlcUA(2S)-GalNAc(6S), and/or IdoUA(2S)-GalNAc(6S), IdoUA(2S)-GalNAc(4S) and novel GlcUA(2S)-GalNAc(4S), where 2S, 4S, and 6S represent 2-O-, 4-O- and 6-O-sulfate, respectively. The CS/DS chains bound two neurotrophic factors and various growth factors expressed in the brain with high affinity as evaluated for the major fraction by kinetic analysis using a surface plasmon resonance detector, and also promoted the outgrowth of neurites of both an axonic and a dendritic nature. The neuritogenic activity was abolished completely by digestion with chondroitinase ABC, AC-I, or B, suggesting the importance of both GlcUA- and IdoUA-containing moieties. It also showed anti-heparin cofactor II activity comparable to that exhibited by DS from porcine skin. Thus, by virtue of its unique structure and biological activities, DS will find a potential use in therapeutics.

Animals↗
PubMed2006

Neuritogenic activity of chondroitin/dermatan sulfate hybrid chains of embryonic pig brain and their mimicry from shark liver. Involvement of the pleiotrophin and hepatocyte growth factor signaling pathways.

Accumulating evidence suggests the involvement of chondroitin sulfate (CS) and dermatan sulfate (DS) hybrid chains in the brain's development and critical roles for oversulfated disaccharides and IdoUA residues in the growth factor-binding and neuritogenic activities of these chains. In the pursuit of sources of CS/DS with unique structures, neuritogenic activity, and therapeutic potential, two novel CS/DS preparations were isolated from shark liver by anion exchange chromatography. The major (80%) low sulfated and minor (20%) highly sulfated fractions had an average molecular mass of 3.8-38.9 and 75.7 kDa, respectively. Digestion with various chondroitinases (CSases) revealed a large panel of disaccharides with either GlcUA or IdoUA scattered along the polysaccharide chains in both of the fractions. The higher M(r) fraction, richer in IdoUA(2-O-sulfate)alpha1-3GalNAc(4-O-sulfate) and GlcUAbeta/IdoUAalpha1-3GalNAc(4,6-O-disulfate) units, exerted greater neurite outgrowth-promoting (NOP) activity and better promoted the binding of various heparin-binding growth factors, including pleiotrophin (PTN), midkine, recombinant human heparin-binding epidermal growth factor-like growth factor, VEGF(165), fibroblast growth factor-2, fibroblast growth factor-7, and hepatocyte growth factor (HGF). These activities were largely abolished by digestion with CSase ABC or B but only moderately affected by a mixture of CSases AC-I and AC-II. In addition, the NOP activity of the larger fraction was markedly reduced by desulfation with alkali, suggesting a role for the 2-O-sulfate of IdoUA(2-O-sulfate)alpha1-3GalNAc(4-O-sulfate). The NOP activity of the higher molecular weight fraction and that of the embryonic pig brain-derived CS/DS fraction were also sup pressed to a large extent by antibodies against HGF, PTN, and their individual receptors cMet and anaplastic lymphoma kinase, revealing the involvement of the HGF and PTN signaling pathways in the activity.

Animals↗
PubMed2005

Humoral defence improvement and haematopoiesis stimulation in sows and offspring by oral supply of shark-liver oil to mothers during gestation and lactation.

Shark-liver oil (SLO) contains two bioactive lipids: alkylglycerols and n-3 PUFA. Alkylglycerols have immunostimulating and haematopoietic properties, while n-3 PUFA are essential for optimal neonatal development. We investigated the beneficial effects of dietary supplementation with 32 g SLO/d to twelve pregnant and then lactating sows (from day 80 of pregnancy to weaning) on the growth and immune status of their offspring, compared with a control group. Sows were vaccinated against Aujeszky's disease 21 d before term. Blood samples were collected from sows before treatment, on delivery and 14 d later, and from five piglets per litter on days 2, 21 and 36 after birth; colostrum and milk samples were collected 12 h, 14 and 28 d postpartum. Compared with controls, supplemented sows had higher levels of both erythrocytes and Hb in their blood, and higher concentrations of IgG, alkylglycerols and n-3 PUFA in their mammary secretions. In piglets from supplemented sows, leucocytes and IgG were higher. Supplementation with SLO resulted in an increase in Aujeszky antibodies in both blood and colostrum of sows after vaccination, together with an increase in Aujeszky antibodies in piglet blood. Our findings demonstrate that improvement of both passive and active immune status in piglets is related to the consumption of alkylglycerols associated with n-3 PUFA in the sow diet. The overall improvement in offspring health status by SLO supplementation to the mother could be of interest for optimisation of the lipid diet during and after pregnancy.

Administration, Oral↗
PubMed2002

Effect of squalene and shark liver oil on serum cholesterol level in hamsters.

Squalene (SQ) and shark liver oil (SLO) are popularly sold as health supplements. The present study was designed to test the hypercholesterolemic activities of pure SQ and SLO in hamsters. SQ was supplemented in diets at the levels of 0.05, 0.1 and 0.5% while SLO was added in the diet at 0.05% by weight. When compared with the control group, serum total cholesterol (TC) was elevated by 32% in the 0.05%SQ group, by 23% in the 0.10%SQ group, by 35% in the 0.5%SQ group and by 19% in the 0.05%SLO group, respectively. The similar trend was observed for serum triglycerides (TG). SQ or SLO feeding also elevated hepatic cholesterol by 97-133% in the four tested groups compared with the control hamsters. In addition, supplementations of SQ and SLO in diets caused significant accumulation of SQ in the liver and adipose tissue. The present results suggest that SQ and SLO are hypercholesterolemic at least in hamsters. Caution has to be taken when SQ or SLO are routinely consumed as health supplements.

Adipose Tissue↗
PubMed1997

A comparison of the hydroxyl radical scavenging properties of the shark bile steroid 5 beta-scymnol and plant pycnogenols.

The hydroxyl radical (OH.) quenching abilities of the following compounds were compared in the deoxyribose degradation system (initiated by the ferrous-ascorbate Fenton reaction): (a) 5 beta-scymnol, the hepatoprotective shark bile sterol, and its mono- and di-sulfate esters; (b) three marketed pycnogenol preparations (syn: proanthocyanidin--natural plant-derived polyphenolic bioflavonoids) extracted from pine tree (Pinus maritima) bark and grape (Vitis vinifera) seeds; and (c) two known hydroxyl radical scavengers, dimethyl sulfoxide and mannitol, and the peroxyl radical scavenger Trolox (the alpha-tocopherol analogue). 5 beta-scymnol was a more potent OH. quencher than dimethyl sulfoxide, mannitol and Trolox, and markedly more potent than the pycnogenol preparations. Increased sulfation of 5 beta-scymnol progressively reduced its free radical scavenging activity, thus clearly attributing the potent OH. quenching properties to its novel tri-alcohol-substituted aliphatic side chain. The favourable interaction of these bile steroids with reactive oxygen species in an aqueous environment, makes them attractive candidates for evaluation as protective agents against disorders in which oxidative stress is implicated.

Animals↗
PubMed1997

The unusual tetrasaccharide sequence GlcA beta 1-3GalNAc(4-sulfate)beta 1-4GlcA(2-sulfate)beta 1-3GalNAc(6-sulfate) found in the hexasaccharides prepared by testicular hyaluronidase digestion of shark cartilage chondroitin sulfate D.

Eight hexasaccharide fractions were isolated from commercial shark cartilage chondroitin sulfate D by means of gel filtration chromatography and HPLC on an aminebound silica column after exhaustive digestion with sheep testicular hyaluronidase. Capillary electrophoresis of the enzymatic digests as well as one- and two-dimensional 500 MHz 1H-NMR spectroscopy demonstrated that these hexasacchrides share the common core saccharide structure GlcA beta 1-3GalNAc beta 1-4 GlcA beta 1-3GalNAc beta 1-4GlcA beta 1-3GalNAc with three, four, or five sulfate groups in different combinations. Six structures had the same sulfation profiles as those of the unsaturated hexasaccharides isolated from the same source after digestion with chondroitinase ABC (Sugahara et al., Eur. J. Biochem., 293, 871-880, 1996) and the other two have not been reported so far. In the new components, a D disaccharide unit, GlcA(2-sulfate)beta 1-3GalNAc(6-sulfate), characteristic of chondroitin sulfate D was arranged on the reducing side of an A disaccharide unit, GlcA beta 1-3GalNAc(4-sulfate), forming an unusual A-D tetrasaccharide sequence, GlcA beta 1-3GalNAc(4-sulfate)beta 1-4GlcA(2-sulfate)beta 1-3GalNAc(6-sulfate) which is known to be recognized by the monoclonal antibody MO225. These findings support the notion that the tetrasaccharide sequence, GlcA beta 1-3GalNAc(4-sulfate)beta 1-4GlcA beta 1-3GalNAc(6-sulfate) is included in the acceptor site of a hitherto unreported 2-O-sulfotransferase responsible for its synthesis. The sulfated hexasaccharides isolated in this study will be useful as authentic oligosaccharide probes and enzyme substrates in studies of sulfated glycosaminoglycans.

Animals↗
PubMed1998

Purification and characterization of the main pepsinogen from the shark, Centroscymnus coelolepis.

The main pepsinogen from the mucosa of the shark, Centroscymnus coelolepis, has been purified and characterized. This zymogen, the most abundant protein in terms of quantity and activity (yield 72%), is a homogeneous monomer of molecular weight 42+/-0.7 kDa, as determined by electrophoresis. The aspartyl proteinase nature of this enzyme was confirmed by the considerable inhibition by pepstatin. Its specificity as to the oxidized B-chain of bovine insulin was determined using electrospray ionization mass spectrometry (ESI-MS) coupled with reversed phase high pressure liquid chromatography (RP-HPLC). The 15-16 Leu-Tyr bond was rapidly cleaved in this substrate, followed by the 24-25 Phe-Phe, 25-26 Phe-Tyr, and 11-12 Leu-Val bonds.

Amino Acid Sequence↗