Chemical Biology & Drug Design

KOLASKAR, A.S.; RAMABRAHMAM, V.; SOMAN, K.V.

doi: 10.1111/j.1399-3011.1980.tb02929.xpmid: 7440058

A simple algorithm has been developed to detect β‐bends and ‘loops’‐chain reversals containing five amino acid residues, using only coordinates of Cα‐atoms from crystal structure data of globular proteins using the above algorithm. Analysis of bends have showed that the total number of bends in each protein (TB) is linearly related to total number of non‐hydrophobic residues in that protein which in turn is related linearly to total number of amino acid residues. Secondly, we found that a large number of consecutive bends occur in each protein which give rise to on an average only three independent residues per turn. Positional preference of amino acid residues in chain reversals is stressed. Consideration of pairs of amino acid residues in positions (i + 1) and (i + 2) of bends seems to provide a more reliable basis for predicting chain reversals in proteins.

SCHWENKE, KLAUS DIETER; SCHULTZ, MANFRED; LINOW, KARL‐JOACHIM; GAST, KLAUS; ZIRWER, DIETRICH

doi: 10.1111/j.1399-3011.1980.tb02930.xpmid: 7440059

The 12S globulin, one of the major storage proteins of rapeseeds, has the following physico‐chemical constants, as determined by ultracentrifugation, quasi‐elastic light scattering measurements and gel chromatography: sedimentation coefficient s020, w= 12.7 times 10‐13 s; diffusion coefficient (quasi‐elastic light scattering) D020, w= 3.8 × 10‐7 cm2 s‐1; Stokes radius (by quasi‐elastic light scattering) Rs= 5.7 nm and (by gel chromatography) Rs= 5.5 nm; partial specific volume (calculated from the amino acid composition) v̄= 0.729 mlg‐1; molecular weight Ms, D = 300, 000 daltons, Ms, Rs= 294,000 daltons (Rs from the gel chromatography); frictional ratio f/fo = 1.28.

NISHIKAWA, KEN; OOI, TATSUO

doi: 10.1111/j.1399-3011.1980.tb02931.xpmid: 7440060

The number of amino acid residues in contact with a residue in a globular protein is a simple and good measure to show the relative location of the residue on the surface or in the interior of the protein. The contact number is estimated as the number of Cα atoms within a sphere of radius r (8 A) centered at the Cα atom of a given residue. The predictor: of a diagram (the plot of the contact number against the residue number) from a given amino acid sequence may be meaningful as an alternative to the secondary‐structure prediction currently performed. Parameter values are determined empirically using the observed contact numbers calculated from known structures of 39 proteins. In order to assess the real efficiency of the method, the prediction has been performed in the following way; all the proteins are divided into two groups; one group is used to derive parameter sets and the other serves to test the prediction accuracy. The test reveals that the parameter sets empirically determined are biased significantly towards the data base, the extent of which is roughly proportional to the number of parameter terms included. The results show that an adequate smoothing of a parameter set is the best way to reduce the extent of biasing towards the data base and to give the best prediction for ‘unknown’ proteins. The prediction accuracy finally obtained is about 0.4 (or roughly 70%), on the average, measured by the correlation coefficient between the predicted and observed diagrams. This value is of the same order as the accuracy in the current predictions of secondary structures.

YAJIMA, HARUAKI; TAKEYAMA, MASAHARU; KOYAMA, KANAME; TOBE, TAKAYOSHI; INOUE, KAZUTOMO; KAWANO, TAMOTSU; ADACHI, HIDEKI

doi: 10.1111/j.1399-3011.1980.tb02932.xpmid: N/A

The octacosapeptide amide corresponding to the entire amino acid sequence of chicken VIP was synthesized in a conventional manner, using a new arginine derivative, NG ‐mesitylene‐2‐sulfonylarginine, Arg(Mts). Treatment of a fragment, Z(OMe)‐Thr‐Asp‐Asn‐Tvr‐NHNH2 with methanesulfonic acid or HBr was found to give a product with a low recovery of Asp, after aminopeptidase digestion. Ring closure of the Asp‐Asn unit seemed to be responsible for this phenomenon. Deprotection with HF or TFA exhibited definitely less such a tendency. In the final step of the synthesis, all protecting groups, including the Mts group, were removed by HF in the presence of m‐cresol and the deprotected peptide was purified by ion‐exchange chromatography on CM‐cellulose followed by isoelectric focusing in Ampholine pH 9–11. Synthetic peptide exhibited the identical Rf value with that of natural chicken VIP and was active as the natural peptide.

VICENTINI, CHIARA B.; VERONESE, AUGUSTO C.; GIORI, PAOLO; BARALDI, PIER GIOVANNI; GUARNERI, MARIO

doi: 10.1111/j.1399-3011.1980.tb02933.xpmid: 7440062

4‐Oximino‐pyrazol‐5‐ones 2a, b and their esters with N‐protected amino acids 3a, b have been studied for carboxyl activation in peptide synthesis. 2a, b and 3a, b appear to be diastereoisomeric mixtures whose configurations have been assigned on the basis of spectroscopic and X‐ray data. Some peptides obtained using these pyrazolone derivatives are reported: no racemization was noted by the Weig and test.

ROY, J.; JOHNSON, M.; GAZIS, D.; SCHWARTZ, I.L.

doi: 10.1111/j.1399-3011.1980.tb02934.xpmid: 7192272

In a continued effort to determine the importance of the hydrogen bonds for stabilization of the biologically active conformation of oxytocin, deamino‐[9‐glycolicamide] oxytocin was synthesized in order to study, in this respect, the hydrogen bond between the peptide N‐H of Gly9 and the C=O of Cys6. In this analog the amide linkage between residues at positions 8 and 9 is replaced by an ester. Thus, the residue at position 9 cannot be involved in hydrogen bond formation with the C=O of Cys6. Deamino‐[9‐glycolicamide] oxytocin exhibited 134 ± 13 U/mg and 355 ± 48 U/mg of uterotonic activity in absence and in presence, respectively, of Mg2+, 108 ± 8 U/mg of milk‐ejecting activity, 0.35 ± 0.03 U/mg of pressor activity and 2.5 ± 0.1 U/mg of antidiuretic activity. It is concluded that the hydrogen bond under question is not critical for the conformation required for biofunctional interaction of oxytocin with its receptors in the uterus, mammary gland and other target organs.

YASUTAKE, AKIRA; MIYAZAKI, KOICHI; AOYAGI, HARUHIKO; KATO, TETSUO; IZUMIYA, NOBUO

doi: 10.1111/j.1399-3011.1980.tb02935.xpmid: N/A

Four stereoisomers of a cyclic depsidipeptide containing a lysine and a 2‐hydroxy‐3‐phenylpropanoic acid (Hpp) residue have been synthesized and their susceptibility toward trypsin examined. Trypsin hydrolyzed cyclo(‐L‐Lys‐L‐Hpp‐) (I‐LL) and cyclo (‐L‐Lys‐D‐Hpp‐) (I‐LD) rapidly and cyclo(‐D‐Lys‐L‐Hpp‐) (I‐DL) and cyclo(‐D‐Lys‐D‐Hpp‐) (I‐DD) very slowly. Proteolytic coefficients of these substrates and a reference compound are shown as follows: I‐LL, 112; I‐LD, 34; I‐DL, 0.34; I‐DD, 0.11, and Ac‐L‐Lys‐OEt, 44. Possible mode of action of trypsin on these substrates was discussed.

FERRARA, PASCUAL; LI, CHOH HAO

doi: 10.1111/j.1399-3011.1980.tb02936.xpmid: N/A

An assay system is described to measure the specific binding of β‐endorphin to opiate sites (receptors) in rat brain membrane preparations using the tritiated hormone as the primary ligand. By this assay procedure, the radioreceptor activity of β‐endorphin and synthetic analogs with various chain lengths has been determined. The results suggest that both NH2‐ and COOH‐terminal sequences of the molecule are involved in the interaction of β‐endorphin with opiate receptors.

YAMASHIRO, DONALD; FERRARA, PASCUAL; LI, CHOH HAO

doi: 10.1111/j.1399-3011.1980.tb02937.xpmid: 6254896

Four analogs of human β‐endorphin (βh‐EP) have been synthesized: [Gly31]‐βh‐EP‐Gly‐NH2, [CH3(CH2)4NH312]‐βh‐EP, [Gly31]‐βh‐EP‐Gly‐Gly‐NH2, and [Gln8, Gly31]‐βh‐EP‐Gly‐Gly‐NH2. All are more active than βh‐EP in an opiate receptor binding assay. Stepwise extension at the COOH‐terminus shows a progressive increase in binding activity. The last analog, which combines extension at the COOH‐terminus with elimination of the remaining anionic charge in βh‐EP, is nine times more active than the parent molecule.

YAMASHIRO, DONALD; FERRARA, PASCUAL; LI, CHOH HAO

doi: 10.1111/j.1399-3011.1980.tb02938.xpmid: 6254897

Des‐acetylated salmon endorphin and turkey β endorphin have been synthesized by the solid‐phase method. Relative opiate activities in a radioreceptor binding assay are: human β‐endorphin, 100; des‐acetylated salmon endorphin, 169; turkey β‐endorphin, 94. Thus, non‐mammalian endorphins can show high activity in a mammalian assay system.