99092-04-3Relevant articles and documents
C11/C9 helices in crystals of αβ hybrid peptides and switching structures between helix types by variation in the α-residue
Basuroy, Krishnayan,Karuppiah, Vasantham,Balaram, Padmanabhan
supporting information, p. 4614 - 4617 (2015/04/14)
Close-packed helices with mixed hydrogen bond directionality are unprecedented in the structural chemistry of α-polypeptides. While NMR studies in solution state provide strong evidence for the occurrence of mixed helices in (ββ)n and (αβ)
The structural characterization of folded peptides containing the conformationally constrained β-amino acid residue β 2,2Ac6c
Basuroy, Krishnayan,Karuppiah, Vasantham,Shamala, Narayanaswamy,Balaram, Padmanabhan
, p. 2589 - 2603 (2013/03/13)
Backbone alkylation has been shown to result in a dramatic reduction in the conformational space that is sterically accessible to α-amino acid residues in peptides. By extension, the presence of geminal dialkyl substituents at backbone atoms also restricts available conformational space for β and γ residues. Five peptides containing the achiral β2,2- disubstituted β-amino acid residue, 1-(aminomethyl)cyclohexanecarboxylic acid (β2,2Ac6c), have been structurally characterized in crystals by X-ray diffraction. The tripeptide Boc-Aib-β 2,2Ac6c-Aib-OMe (1) adopts a novel fold stabilized by two intramolecular H-bonds (C11 and C9) of opposite directionality. The tetrapeptide Boc-[Aib-β2,2Ac 6c]2-OMe (2) and pentapeptide Boc-[Aib-β 2,2Ac6c]2-Aib-OMe (3) form short stretches of a hybrid αβ C11 helix stabilized by two and three intramolecular H-bonds, respectively. The structure of the dipeptide Boc-Aib-β2,2Ac6c-OMe (5) does not reveal any intramolecular H-bond. The aggregation pattern in the crystal provides an example of an extended conformation of the β2,2Ac6c residue, forming a 'polar sheet' like H-bond. The protected derivative Ac-β2,2Ac6c-NHMe (4) adopts a locally folded gauche conformation about the Cβi?￡?C α bonds (θ=-55.7°). Of the seven examples of β2,2Ac6c residues reported here, six adopt gauche conformations, a feature which promotes local folding when incorporated into peptides. A comparison between the conformational properties of β2,2Ac6c and β3,3Ac6c residues, in peptides, is presented. Backbone torsional parameters of H-bonded αβ/βα turns are derived from the structures presented in this study and earlier reports. Copyright
Preparation and structure of β-peptides consisting of geminally disubstituted β2,2- and β3,3-amino acids: A turn motif for β- peptides
Seebach, Dieter,Abele, Stefan,Sifferlen, Thierry,Haenggi, Martin,Gruner, Sibylle,Seiler, Paul
, p. 2218 - 2243 (2007/10/03)
We report on the synthesis of new and previously described β-peptides (1-6), consisting of up to twelve β2,2- or β3,3-geminally disubstituted β-amino acids which do not fit into any of the secondary structural patterns of β-peptides, hitherto disclosed. The required 2,2- and 3,3-dimethyl derivatives of 3-aminopropanoic acid are readily obtained from 3-methylbut-2-enoic acid and ammonia (Scheme 1) and from Boc-protected methyl 3-aminopropanoate by enolate methylation (Scheme 2). Protected (Boc for solution-, Fmoc for solid-phase syntheses) 1- (aminomethyl)cycloalkanecarboxylic-acid derivatives (with cyclopropane, cyclobutane, cyclopentane, and cyclohexane rings) are obtained from 1- cyanocycloalkanecarboxylates and the corresponding dihaloalkanes (Scheme 3). Fully 13C- and 15N-labeled 3-amino-2,2-dimethylpropanoic-acid derivatives were prepared from the corresponding labeled precursors (see asterixed formula numbers and Scheme 4). Coupling of these amino acids was achieved by methods which we had previously employed for other β-peptide syntheses (intermediates 18-23). Crystal structures of Boc-protected geminally disubstituted amino acids (16a-d) and of the corresponding tripeptide (23a), as well as NMR and IR spectra of an isotopically labeled β-hexapeptide (2a*) are presented (Figs. 1-4) and discussed. The tripeptide structure contains a ten-membered H-bonded ring which is proposed to be a turn-forming motif for β-peptides (Fig. 2).
