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C M Deber

Publications and source records attributed to C M Deber.

96 records · Page 6Linked to original sources
PubMed1972

Conformational interconversions of the cyclic hexapeptide cyclo(Pro-Gly) 3 .

A cyclic hexapeptide, cyclo(Pro-Gly-Pro-Gly-Pro-Gly), has been synthesized; its solution conformations were examined by 220-MHz nuclear magnetic resonance spectroscopy. The solution structures have been deduced, and shown to vary as a function of solvent polarity. In addition, it has been found that this cyclic peptide binds alkali metal cations. While the predominant conformation of this cyclic peptide is 3-fold symmetric in the apolar solvent methylene chloride, an asymmetric structure is preferred in some polar solvents (water, dimethylsulfoxide). However, addition of alkali metal salts, such as sodium thiocyanate, to dimethylsulfoxide solutions of the peptide shifts the conformational equilibrium in favor of a second type of C(3)-symmetric structure, presumably the result of the formation of a stable peptide-metal ion complex. Nuclear magnetic resonance data suggest that the peptide in methylene chloride solution takes up a conformation containing three cis' Pro C(alpha)-C=O bonds and three cis Gly-Pro peptide bonds; that water and dimethylsulfoxide stabilize a conformer in which one (or two) sets of such bonds of a given Pro-Gly unit have undergone interconversion to trans'/trans forms; and that alkali metal cations complex the cyclic peptide in a C(3)-symmetric all-trans'/trans structure.

Butanols↗
PubMedDate not supplied

Influence of glycine residues on peptide conformation in membrane environments.

Transmembrane (TM) segments of integral membrane proteins are putatively alpha-helical in conformation, yet their primary sequences are rich in residues known in globular proteins as helix-breakers (Gly) and beta-sheet promoters (Ile, Val, Thr). To examine the specific 2 degrees structure propensities of such residues in membrane environments, we have now designed and synthesized a series of model 20-residue peptides with "guest" hydrophobia segments embedded in "host" N- and C-terminal hydrophilic matrices. Molecular design was based on the prototypical sequence NH2-(Ser-Lys)2-Ala5-Leu6-x7-Ala8-Leu9-y10-Trp 11-Ala12-Leu13-z14-(Lys-Ser)3-OH. The 10-residue hydrophobic mid-segment 5-14 is expected to act as ca. three turns of an alpha-helix. In the present work, we compare the 20-residue peptide having three "helix-forming" Ala residues [x = y = z = Ala (peptide 3A)] to the corresponding peptide 3G (x = y = z = Gly) which contains three "helix-breaking" Gly residues. Trp was inserted to provide a measure of aromatic character typical of TM segments; Ser and Lys enhanced solubility in aqueous media. Circular dichroism studies in water, in a membrane-mimetic [sodium dodecylsulfate (SDS)], medium, and in methanol solutions, demonstrated the exquisite sensitivity of the conformations of these peptides to environment, and proved that despite its backbone flexibility, Gly can be accommodated as readily as Ala into a hydrophobic alpha-helix in a membrane. Nevertheless, the relative stability of Ala- vs. Gly-containing helices emerged in methanol solvent titration and temperature dependence experiments in SDS.(ABSTRACT TRUNCATED AT 250 WORDS)

Buffers↗
PubMedDate not supplied

Conformational origin of a difficult coupling in a human growth hormone releasing factor analog.

During the solid-phase synthesis of the human growth hormone releasing factor (GRF) analog [Ala15, Leu27, Asn28] -GRF(1-32)-OH, incorporation of Boc-Gln16 was determined to be incomplete. While aggregation of growing resin-bound peptide chains with concomitant beta-sheet formation and "precipitation" has been proposed to account in general for such "difficult coupling," no feature of sequence in the Gln16 region of this GRF analog provided an immediate rationale for this result. We now report 500 MHz 1H NMR spectra of a series of resin-bound GRF segments surrounding the Gln16 position (19-32 through 14-32), swelled in dimethylsulfoxide-d6 solutions [GRF(14-32) = Leu14-Ala-Gln-Leu-Ser(Bzl)-Ala-Arg(Tos)-Lys(CIZ)-Leu- Leu-Gln-Asp(OcHex)-Ile-Leu-Asn-Arg(Tos)-Gln-Gln-Gly32-PAM resin]. While relatively sharp spectra are observed for GRF(19-32), components with resonances broadened by an order-of-magnitude appear in spectra of the 18-32 and 17-32 peptide-resin, and the entire spectrum of 16-32 is ill-resolved and highly broadened. Subsequent spectra sharpen again (15-32, 14-32). These combined synthesis/spectroscopic experimental results, in conjunction with predictive analyses using standard Chou-Fasman 2 degrees structure parameters, suggest that the completeness of the Gln16 coupling is hindered by formation of a specific, folded beta-sheet/beta-turn structure in GRF(16-32) (with the turn located at 18-21, "upstream" of the difficult coupling site), and accompanying aggregation of peptide chains. This analysis suggests that awareness of such potential beta-sheet/beta-turn sequences can guide analog choices, and/or facilitate pre-programming of synthesis steps in anticipation of problem couplings.

Amino Acid Sequence↗