Transfer hydrogenation; a convenient method for removal of some commonly used protecting groups in peptide synthesis

N-Benzyloxycarbonyl and benzyl ester groups in peptidescan be conveniently removed by transfer hydrogenation with cyclohexene and 10% palladium-carbon catalyst. If freshly prepared palladium black catalyst is used, other commonly used protecting groups like Nτ-benzyl (histidine), benzyl ether (tyrosine, serine), and nitro (arginine) can also be removed much more rapidly than in the case of the usually employed catalytic hydrogenation

Silicon tetrachloride and phenol as N(α)-t-butoxycarbonyl group deprotecting agent in solid phase peptide synthesis

The combination of 1M silicon tetrachloride and 3M phenol serves as an efficient N(α)-t-butoxycarbonyl deblocking agent in solid phase peptide synthesis, the duration of the cleavage being 10 min. This is demonstrated by the synthesis of the naturally occurring μ-receptor selective opioid heptapeptide, dermorphin

Pharmacological activities of some synthetic peptides related to dermorphin

Objectives: To investigate the relationship between the structure of demorphins (DM) and their pharmacological properties, six analogues of Hyp6DM and Pro6DM were synthesised and their biological activities were studied. Methods: The peptides were synthesised by the solid phase method using 9-fluorenylmethoxycarbonyl amino acid trichlorophenyl esters as coupling agents and Merrifield resin as solid support. The opioid agonist activity was studied using co-axially, electrically stimulated contraction of isolated guinea pig ileum (GPI, in vitro). Their analgesic activity was assessed in mice using Eddy's hot plate method and tail-flick method. The antidiarrhoeal activity was determined by the charcoal meal test in mice. Results: In the GPI assay, the synthetic analogues possess agonistic activity that are less pronounced than morphine. Peptides I and II (substitution of ser of position 7 and Gly at position 4 in Hyp6DM series respectively) possessed considerable analgesic activity but are almost inactive in the GPI assay. Peptide III (Pro6, Sar7DM) possess only analgesic activity. In GPI assay, peptide IV was inactive. Peptide V and VI had equipotent analgesic and antidiarrhoeal activity. Conclusion: Peptides with various structures can possess specificities that may prove useful in biological applications. Among them Sar4, Hyp6, Tyr7DM, Hyp6, Pro7DM, Pro6, Sar DM and Phg3, ProDM exhibited a high degree of selectivity in their activities

Solid phase synthesis of the protected peptide sequence (12-​16) of human fibrinopeptide A

The title H-​Gly-​Gly-​Gly-​Arg(NO2)​-​OMe (I) was prepd. by a solid-​phase method in which both Me3CO2C (BOC) and o-​O2NC6H4S (Nps) amino acids were used. R-​Gly-​Gly-​Gly-​Arg(NO2)​-​resin (R = BOC, Nps) were prepd. and cleaved with MeOH and Et3N to give R-​Gly-​Gly-​Gly-​Arg(NO2)​-​OMe (II) in yields of 52.5​% for R = BOC and 36​% for R = Nps. II was deprotected with HCl to give I

Catalytic transfer hydrogenation in synthesis of substance P

Substance P, H-​Arg-​Pro-​Lys-​Pro-​Gln-​Gln-​Phe-​Phe-​Gly-​Leu-​Met-​NH2, was prepd. by stepwise couplings in soln. using catalytic transfer hydrogenation for removal of benzyloxycarbonyl and nitro protecting groups. Formic acid was used as H donor and Pd was used as the catalyst

Fibrinopeptides. II. Synthesis of protected hexapeptide sequence (5-​10) of human fibrinopeptide-​A

The protected hexapeptide sequence (5-​10) of human fibrinopeptide-​A, BOC-​Glu(OBzl)​-​Gly-​Asp(OBzl)​-​Phe-​Leu-​Ala-​OMe (BOC = Me3CO2C, Bzl = PhCH2) (I)​, was synthesized using the mixed anhydride (MA)​, dicyclohexylcarbodiimide (DCC)​, 2,​4,​5-​trichlorophenyl ester (OCP) and pentachlorophenyl ester (OPCP) methods. The OCP method was applicable only after the tripeptide stage. The overall yield of I from the DCC, MA and OPCP methods was 23.2, 20.5 and 18.7​%, resp

Fibrinopeptides. Iii. Synthesis of the Protected Nonapeptide Sequence of Fibrinopeptide-B of Green Monkey

The protected nonapeptide, Z-Asn-Glu(OBzl)-Glu(OBzl)-Gly-Leu-Phe-Gly-Gly- Arg(NO2)OMe, corresponding to the amino acid sequence present in fibrinopeptide-B of green monkey, has been synthesised by conventional methods

Synthesis of the Pentadecapeptide Sequence of the Active Site of Rabbit Muscle Triosephosphate Isomerase

The pentadecapeptide fragment, Trp-Val-Leu-Ala-Tyr-Glu-Pro-Val-Trp-Ala-Ile-Gly-Thr-Gly-Lys, which constitutes a part of the active site of rabbit muscle triosephosphate isomerase has been synthesized. It does not exhibit any catalytic activity typical of triosephosphate isomerase

Peptides related to physalaemin-​III

Four octapeptide analogs, Pro-​Asn-​Pro-​Phe-​Phe-​Gly-​Leu-​Met-​NH2 [65535-​22-​0]​, Pro-​Gln-​Pro-​Phe-​Phe-​Gly-​Leu-​Met-​NH2 [65535-​23-​1]​, Pro-​Asn-​Tyr-​Phe-​Phe-​Gly-​Leu-​Met-​NH2 [65535-​24-​2]​, and Pro-​Gln-​Tyr-​Phe-​Phe-​Gly-​Leu-​Met-​NH2 [65535-​25-​3] corresponding to the C-​terminal sequence of physalaemin [2507-​24-​6] were synthesized in the solid phase using Boc-​amino acid active esters in the presence of 1-​hydroxybenzotriazole. The acidic amino acid tyrosine at position 8 and the basic lysine at position 6 could be replaced by neutral amino acids without much loss of activity (contraction of guinea pig ileum)​. But replacement of the basic amino acid lysine at position 6 by an acidic amino acid, tyrosine, decreased the activity

Solid-​phase synthesis of the hexapeptide sequence of the active site of triosephosphate isomerase

Solid phase synthesis of the protected hexampeptide, Z-​Ala-​Tyr-​Glu(OCH2Ph)​-​Pro-​Val-​Trp-​OCH2Ph (II, Z = PhCH2O2C)​, was reported. This peptide was released from the peptide polymer by transesterification with PhCH2OH in Et3N at 60°. Hydrogenation of II over Pd black yields Ala-​Tyr-​Glu-​Pro-​Val-​Trp, part of the active site of the enzyme, triosephosphate isomerase