Characterization of b-Turn and Asx-Turns Mimicry in a Model Peptide: Stabilization via CH O Interaction A. K. Thakur R. Kishore Institute of Microbial Technology, Sector 39-A, Chandigarh 160 036, India Received 24 October 2005; revised 8 December 2005; accepted 8 December 2005 Published online 12 January 2006 in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/bip.20441 Abstract: The chemical synthesis and single-crystal X-ray diffraction analysis of a model peptide, Boc–Thr–Thr–NH 2 (1) comprised of proteinogenic residues bearing an amphiphilic C b -stereogenic center, has been described. Interestingly, the analysis of its molecular structure revealed the exis- tence of a distinct conformation that mimics a typical b-turn and Asx-turns, i.e., the two Thr residues occupy the left- and right-corner positions. The main-chain torsion angles of the N- and C-terminal residues i.e., semiextended: / ¼68.98, w ¼ 128.68; semifolded: / ¼138.18, w ¼ 2.58 conformations, respectively, in conjunction with a gauche disposition of the obligatory C- terminus Thr C g H 3 group, characterize the occurrence of the newly described b-turn- and Asx- turns-like topology. The preferred molecular structure is suggested to be stabilized by an effective nonconventional main-chain to side-chain C i ¼¼O HC g iþ2 -type intraturn hydrogen bond. Noteworthy, the observed topology of the resulting 10-membered hydrogen-bonded ring is essen- tially similar to the one perceived for a classical b-turn and the Asx-turns, stabilized by a conven- tional intraturn hydrogen bond. Considering the signs as well as magnitudes of the backbone tor- sion angles and the orientation of the central peptide bond, the overall mimicked topology resem- bles the type II b-turn or type II Asx-turns. An analysis of Xaa–Thr sequences in high-resolution X- ray elucidated protein structures revealed the novel topology prevalence in functional proteins (unpublished). In view of indubitable structural as well as functional importance of nonconven- tional interactions in bioorganic and biomacromolecules, we intend to highlight the participation of Thr C g H in the creation of a short-range C¼¼O HC g -type interaction in peptides and proteins. # 2006 Wiley Periodicals, Inc. Biopolymers 81: 440–449, 2006 This article was originally published online as an accepted preprint. The ‘‘Published Online’’ date corresponds to the preprint version. You can request a copy of the preprint by emailing the Biopolymers editorial office at biopolymers@wiley.com Keywords: -turn; Asx-turns; mimicry; peptide–protein interaction; chemical synthesis; X-ray diffraction INTRODUCTION In recent years, the design and construction of back- bone secondary structural mimicry and novel non- repetitive secondary structural motifs, frequently ob- served in proteins and peptides, have emerged as important targets for molecular biophysicists and bio- organic chemists. 1–10 The design of well-defined structural mimics and molecular scaffolds, however, necessitates precise knowledge of intrinsic folding– unfolding propensities of various proteinogenic 11–16 as well as nonproteinogenic 17–22 -amino acids, in conjunction with ,-dependent preferred side-chain rotameric distribution. 23–28 Of the 20 encoding amino Correspondence to: R. Kishore; e-mail: kishore@imtech.res.in Biopolymers, Vol. 81, 440–449 (2006) # 2006 Wiley Periodicals, Inc. Contract grant sponsor: Department of Biotechnology and Council of Scientific and Industrial Research (CSIR), India. 440