Tetrapeptides, Cbz‐Gly‐X‐Y‐Gly‐OSt (1–4)—as well as cyclic systems, cyclo[NH‐(CH2)n‐CO‐Gly‐Ser(OX)‐Ser(OX)‐Gly] (5 and 6; n = 4 and 2, X = But or H), have been synthesized in order to compare the CD spectrum of linear and cyclic β‐turn models containing either a protected or a free hydroxyl of the serine residue. In extremely dilute cyclohexane solution the linear models Cbz‐Gly‐Ser‐Y‐Gly‐OSt (1–3a) show class B spectra with very strong positive bands, contrary to other members of the series. Based on 200‐MHz 1H nuclear overhauser enhancement and Fourier transform ir studies, Cbz‐Gly‐Ser‐Ser(OBut)‐Gly‐OSt (3a) in dilute chloroform solution assumes a distorted type II β‐turn conformation fixed by an extended system of intramolecular H bonds. As evidenced by 1H‐nmr and FT‐IR experiments, the cyclic model cyclo[NH‐(CH2)4‐CO‐Gly‐Ser(OBut)‐ Ser(OBut)‐Gly] (5a) in a 1 : 1 mixture of (CD3)2SO‐CDCl3 is also characterized by a type II β‐turn encompassing the Ser3(OBut)‐Gly4 sequence. In water, a class B pattern was measured for this model, in good agreement with theoretical and experimental studies that show that type II β‐turns are generally characterized by class B spectra. In the protected and free OH cyclic models, cyclo[NH‐(CH2)2‐CO‐Gly‐Ser(OX)‐Ser(OX)‐Gly] (5b and 6b, X = But or H) distortions of the peptide backbone due to the loss of two CH2 groups result in the appearance of CD spectra characterized by a strong negative band near 200 nm, interpreted as a sign of the lack of β‐turn structures in these models. This observation, together with other CD data discussed in this paper, clearly show that the CD of serine‐containing β‐turn sequences strongly depends on long‐range backbone and local side‐chain interactions.
ASJC Scopus subject areas
- Organic Chemistry