A cyclic dipeptide in which L-Ala-Gly was cyclized with E-aminocaproic acid has been synthesized as a model for a a-bend. Its conformational properties have been examined by means of conformational energy calculations and nuclear magnetic resonance, infrared, Raman, and circular dichroism spectroscopy in various solvents. These calculations and experiments suggest that a type II a-bend exists in the Ala-Gly moiety, with an NH-O=C hydrogen bond in the E-aminocaproic acid portion of the molecule, and that the molecule adopts a unique conformation in solution. In contrast, an open-chain analog of this compound exists in solution as an ensemble of conformations but with a significant amount of a type II a-bend structure in the ensemble.and Boc-L-Ala-Gly-Aca-OMe (Ac, NHMe, Boc, and OMe designate the acetyl, N-methyl amide, t-butyloxycarbonyl, and methyl ester groups, respectively) were also considered.The cyclic compound is of interest because of the constraints experienced by the Ala-Gly dipeptide moiety. The distance between the Ca and Cf atoms of Aca must be less than 5.0 A.Therefore, any conformation of the Ala-Gly moiety is a bend. The cyclic compound can be used to characterize the properties to be expected for a fl-bend; thus, the spectroscopic techniques mentioned above can be applied to detect fl-bends in future studies of the conformation of any peptide in solution.There is considerable interest in the properties of f-bends in polypeptide chains. A f-bend enables the chain to reverse its direction and adopt a compact globular structure. When present at the surface of a protein, it constitutes a possible recognition site on antigens, antibodies, enzymes, and protein substrates. Because short-range interactions dominate in determining the conformations of polypeptides in general (1) and of f-bends in particular (2), numerous investigations are being carried out to try to detect fl-bends in short oligopeptides that have amino acid sequences that are known to adopt f-bend conformations in globular proteins.Although short oligopeptides probably exist as ensembles of conformations in solution, the dominant species in an ensemble could be a f-bend if the amino acid sequence were one that favored this conformation. From the point of view of examining the biological significance of fl-bends, it is of interest to be able to increase the tendency toward formation of a f-bend in a sequence that already has a significant tendency to adopt this conformation. This can be accomplished by coupling nonpolar groups to the ends of the oligopeptide to enable the resulting hydrophobic bond to stabilize the fl-bend in water, or to solubilize the peptide in nonpolar solvents (3), or by cyclizing a f-structure-for example, with an aliphatic hydrocarbon chain (4).In this paper, we report the results of a study in which cyclization has been used to stabilize a f-bend. For this purpose, we have synthesized the cyclic compound shown in Fig. 1, which we designate as a cyclo-blocked alkane dipeptide, cyclo(L-Ala-Gly-Aca), Aca des...
