STABILIZATION OF A C-7 EQUATORIAL GAMMA-TURN IN DMSO-D(6) BY A DITRYPTOPHAN CROSS-LINK

Covalent crosslinks can control local peptide conformation. In tripept ide sequences of the general formula Cys-Xxx-Cys, cysteine disulfides have been previously shown to enforce a C-7 equatorial gamma-turn conf ormation (also referred to as an inverse gamma-turn). Much less is kno wn about the effects of dityrosine and ditryptophan crosslinks on loca l peptide structure. In a series of tripeptides, ditryptophan crosslin ks were formed using the two-step process of acid-promoted Mannich dim erization followed by oxidative aromatization. In these peptides, with the general formula Trp-Xxx-Trp (Xxx not equal Gly), ditryptophan cro sslinks were found to stabilize a C-7 equatorial gamma-turn conformati on in DMSO-d(6). Rigorous support for a C-7 equatorial conformation in the crosslinked sequence Trp-Pro-Trp came from a variety of H-1 NMR e xperiments and molecular modelling. Interproton distances were derived from NOE buildups that were determined through a series of double pul sed field gradient spin echo (DPFGSE) experiments. In addition, the sm all temperature dependence of the i + 2 NH chemical shifts (Delta delt a/Delta T < 2 ppm/degrees C) provided further support for the intramol ecular hydrogen bond which defines a gamma-turn. (C) 1998 Elsevier Sci ence Ltd. All rights reserved.