organic compounds o212 # 2002 International Union of Crystallography DOI: 10.1107/S0108270101016468 Acta Cryst. (2002). C58, o212±o214 Design of peptides with a,b -dehydro residues: pseudo-tripeptide N-benzyloxycarbonyl±DLeu±L-Ala± L-Leu±OCH 3 Jyoti Makker, Sharmistha Dey, Pravindra Kumar and Tej P. Singh* Department of Biophysics, All India Institute of Medical Sciences, Ansari Nagar, New Delhi 110 029, India Correspondence e-mail: tps@aiims.aiims.ac.in Received 11 June 2001 Accepted 7 December 2001 Online 12 March 2002 The title peptide N-benzyloxycarbonyl±ÁLeu±l-Ala±l-Leu± OCH 3 [methyl N-(benzyloxycarbonyl)-,-dehydroleucyl-l- alanyl-l-leucinate], C 24 H 35 N 3 O 6 , was synthesized in the solution phase. The peptide adopts a type II 0 -turn conformation which is stabilized by an intramolecular 4 ! 1 NÐHO hydrogen bond. The crystal packing is stabilized by two intermolecular NÐHO hydrogen bonds. Comment The conformational preferences of amino acid side chains govern the folding of peptides. These preferences differ from one amino acid to another, as observed in protein crystals (Chandrasekaran & Ramachandran, 1970; Janin et al., 1978; Bhat et al., 1979) and oligopeptides (Benedetti et al., 1983), and as determined theoretically by means of conformational energy computations (Zimmerman et al., 1977; Vasquez et al., 1983). Short-range interactions involving the atoms of the side chains with the atoms of the backbone, as well as the atoms of the two neighbouring peptide units, determine the confor- mational preferences in peptides. Thus, the peptides can adopt a large number of conformations in order to gain preferred side-chain±backbone and side-chain±side-chain interactions. This makes the design strategy rather weak and impractical. In order to develop an effective design tool, it is necessary to restrict the number of preferred conformations to a minimum. This can be achieved through introduction of well de®ned steric constraints with ,-dehydro residues. So far, it has been shown that the dehydro residues, such as dehydrophenyl- alanine (ÁPhe), dehydroleucine (ÁLeu) and dehydro-- aminobutyric acid (ÁAbu), induce a type II -turn confor- mation when placed at the (i+2) position (Singh & Narula, 1996). However, the conformational contributions of these dehydro residues when placed at the (i+1) position have not yet been fully de®ned. In order to establish the design rules with ,-dehydro residues at the (i+1) position, a tripeptide, N-benzyloxycarbonyl(Cbz)±ÁLeu±l-Ala±l-Leu±OCH 3 , (III), was synthesized and its three-dimensional structure deter- mined by X-ray diffraction. The structure of peptide Cbz±ÁLeu±l-Ala±l-Leu±OCH 3 shows that the side chain of the ÁLeu residue adopts the expected geometry, with the vinyl H atom on the same side of the adjacent carbonyl group. The C1AÐC1B bond length of 1.322 (5) A Ê is in agreement with the average value of 1.323 (2) A Ê quoted for this bond (Benedetti, 1977). The planarity imposed by the ,-double bond should promote an electronic delocalization, with shrinking of the C1AÐN1 and C1AÐC1P bonds, and lengthening of the carbonyl double bond (Table 1). The C1AÐN1 and C1AÐC1P bond lengths of 1.413 (4) and 1.500 (4) A Ê , respectively, are in accordance with the expected values reported for dehydro residues (Singh & Narula, 1996). The C1PÐO1P bond length of 1.217 (4) A Ê seems to be only slightly in¯uenced by electronic effects. The bond angles N1ÐC1AÐC1P, N1ÐC1AÐC1B and C1AÐ C1BÐC1G in the ÁLeu residue deviate from the standard value of 120  (Table 1). The opening of the C1AÐC1BÐC1G angle helps in releasing the constraints caused by the changes introduced in an amino acid as a result of dehydrogenations at the C1A and C1B atoms. A perspective view of the title molecule is shown in Fig. 1. Selected torsion angles are given in Table 1. The peptide adopts a type II 0 -turn conformation characterized by torsion angles ' 1 = 47.9 (4)  ,  1 = 137.2 (3)  , ' 2 = 87.2 (3)  and Acta Crystallographica Section C Crystal Structure Communications ISSN 0108-2701 Figure 1 A perspective view of the title peptide. Displacement ellipsoids are drawn at the 50% probability level.