ThermalStabilityofDehydrophenylalanine-ContainingModelPeptides asProbedbyInfraredSpectroscopy:aCaseStudyofan a-Helicalanda 3 10 -HelicalPeptide by AlkaGupta a ), RanjanaMehrotra* a ), EvgueniKlimov b ), HeinzWilhelmSiesler b ), RatanmaniM.Joshi c ), and ViranderSinghChauhan c ) a ) Optical Radiation Standards, National Physical Laboratory, Dr. K. S. Krishnan Road, New Delhi 110012, India (e-mail: ranjana@mail.nplindia.ernet.in) b ) Department of Physical Chemistry, University of Duisburg-Essen, Schutzenbahn 70, D-45117 Essen, Germany c ) International Center for Genetic Engineering and Biotechnology, Aruna Asaf Ali Marg, New Delhi 110067, India The temperature-dependent secondary-structural changes in the two known helical model peptides Boc-Val-DPhe-Ala-Leu-Gly-OMe (1; a-helical) and Boc-Leu-Phe-Ala-DPhe-Leu-OMe (2 ; 3 10 -helical), which both comprise a single dehydrophenylalanine ( DPhe) residue, were investigated by means of FT- IR spectroscopy (peptide film on KBr). Both the first-order and the better-resolved second-order derivative IR spectra of 1 and 2 were analyzed. The n(NH) (3240±3340 cm 1 ), the Amide-I (1600 ± 1700 cm 1 ), and the Amide-II (1510 ± 1580 cm 1 ) regions of 1 and 2 showed significant differences in thermal-denaturation experiments (228 ! 1448), with the 3 10 -helical peptide (2) being considerably more stable. This observation was rationalized by different patterns and strengths of intramolecular H-bonds, and was qualitatively related to the different geometries of the peptides. Also, a fair degree of residual secondary-structural elements were found even in the -denatured× states above 1048 (1) or 1348 (2). Introduction. ± Peptides containing a,b-dehydro-a-amino acids (DAAs) have recently attracted much attention in view of their potential use in the design of synthetic analogues of biologically important peptides with preferred secondary structures [1]. A number of spectroscopic and physico-chemical techniques have been extensively employed for the conformational analysis of -dehydro peptides×, both in the solid state and in solution. Especially dehydrophenylalanine ( DPhe) has been vastly used in generating specific models of different types of secondary structures, largely helices and turns [1 ± 3]. During the past decade, we have extensively explored the preferential secondary structures of peptides containing DPhe units. It is established now that the introduction of a DPhe moiety usually forces a peptide to adopt a helical fold, mostly of the 3 10 -helical and sometimes of the a-helical type [1 ± 5], provided the peptide has the required minimum number of residues. Since such peptides have been designed and their conformations have been investigated for their potential use as protein mimics, their secondary structures are highly crucial for their biological action. Equally important is the characterization of their disordered states, since loss of ordered structure at higher temperatures often leads to drastic changes in properties such as solubility and biological activity. This has already evoked much interest in the thermal properties of proteins during the past few years [6 ± 11]. For CHEMISTRY & BIODIVERSITY ± Vol. 3 (2006) 284 ¹ 2006 Verlag Helvetica Chimica Acta AG, Z¸rich