1. On the mechanism of pepsin action
T R Hollands, J S Fruton Proc Natl Acad Sci U S A. 1969 Apr;62(4):1116-20. doi: 10.1073/pnas.62.4.1116.
The problem of the mechanism of pepsin action is considered in relation to recent data on the kinetics and specificity of the enzyme, as well as the finding, reported here, that pepsin exhibits a deuterium isotope effect in the cleavage of a peptide bond. The kinetic parameters for the hydrolysis of the Phe(NO(2))-Phe bond of Gly-Gly-Gly-Phe(NO(2))-Phe-OMe by pepsin have been determined in H(2)O and in D(2)O. The finding of a significant deuterium isotope effect (k(H2O)/k(D2O) = ca. 2) supports the hypothesis that the catalytic mechanism of pepsin involves the participation, in the rate-limiting step, of a proton donor (probably an enzymic carboxyl group) in addition to an enzymic carboxylate group acting as a nucleophile.
2. Three protected tetrapeptides
E Fenude, G Casalone Acta Crystallogr C. 1996 Apr 15;52 ( Pt 4):973-8. doi: 10.1107/s0108270195013345.
The structures of three protected tetrapeptides, containing the Boc-Gly-Gly-Phe-X-OMe chain, tert-butoxycarbonyl-glycy-glycl-phenylalanine-leucine methyl ester dihydrate, Boc-Gly-Gly-L-Phe-D-Leu-OMe, C25H38N4O7.2H2O, tert-butoxycarbonyl-glycy-glycl-phenylalanine-methionine methyl ester dihydrate, Boc-Gly-Gly-L-Phe-D-Met-OMe, C24H36N4O7S.2H2O and tert-butoxycarbonyl-glycy-glycl-phenylalanine-norleucine methyl ester dihydrate, Boc-Gly-Gly-D-Phe-L-Nle-OMe, C25H38N4O7.2H2O, are described. The three molecules have the same conformation on the tetrapeptide chain and display the same packing, consisting of couples of molecules linked head-to-tail by two hydrogen (N--H...O) bonds; other hydrogen bonds, also involving two water molecules of crystallization, link these couples together and give rise to a planar structure.
3. [Syntheses of oligopeptides related to the insulin sequence B 22-25 (Arg-Gly-Phe-Phe) (author's transl)]
K Eisele Hoppe Seylers Z Physiol Chem. 1975 Jun;356(6):845-54.
Syntheses of peptides with the sequences Gly-Phe, Gly-Phe-Phe, Arg-Gly-Phe and Arg-Gly-Phe-Phe are described. They were performed with the free acids, methyl esters and caramides. The peptides correspond partially or directly to the insulin sequence B 22 - 25 (Arg-Gly-Phe-Phe), the tetrapeptide amide or tetrapeptide methyl ester of which shows insulin-like activity (l.c.[1,2]). For testing the structural specificity of the arginyl residue, the following peptides were also synthesised: NG-NO2-Arg-Gly-Phe-Phe-NH2 and -OMe, Orn-Gly-Phe-Phe-NH2 and Cit-Gly-Phe-Phe--NH2. In connection with the above, the syntheses of the new derivatives Nalpha,Ndelta-Z2-L-ornithine p-nitrophenyl ester and N-Boc-L-citrulline p-nitrophenyl ester are described. All peptides were synthesised conventionally.
