Synthesis and characterization of poly(LysAla₃)

Abstract

SynopsisThe synthesis and characterization of poly(LysAlaa) are described. The polytetrapeptide is a model for short sequences found in proelastin, and is presumably involved in desmosine or isodesmosine cross-link formation in the native protein. Poly(LysAla3) is found to possess a mixture of conformations in aqueous solution dependent on molecular weight and pH. Low-molecular-weight (ca. 3000) material appears to be a mixture of random and extended helix at neutral pH. However, as the molecular weight is increased an increasing amount of a-helix is observed rising to >50% for mol wt = 21,000. The a-helical chain segments are thermally stable, melting to a mixture of extended and random forms at T, = 25°C. High pH (10.5) promotes further a-helix formation but at pH >11.0 the polypeptide becomes insoluble. The inference is that short chain segments of the peptide in elastin are unlikely to be a-helical in the equilibrium state but may fluctuate through such a conformation.

Water-soluble lysine-containing polypeptides. IV. The synthesis, characterization,and circular dichroism spectra of sequential polypeptides formed from dipeptides of lysine and amino acids of increasing side chain size

“…This conformational assignment is consistent with optical rotatory dispersion studies reported for poly-(L-lys-L-ala) of similar size (26) and closely resembles a series of poly-(L-lys-L-ala) random copolymers (37). Poly-(L-lys-L-ala-L-ala) (38) and poly-(L-lys-L-ala-L-ala-L-ala) (39,40) finite tendencies towards a-helical conformations in conditions of low salt and neutral p H but this may be attributed to a more effective separation of positive charge than is possible with poly-(L-lys-L-ala).…”

Circular dichroism studies of an elastin crosslinked peptide

“…The positive ellipticity bands a t 215 nm and negative bands at 235 and 190 nm are generally regarded as representative of the unordered form. However, more recently similar spectral patterns exhibited by ionized homopolypeptides20 and some copolypeptides in dilute solutions,21 which show as the desmosine peptide a temperature sensitivity of a positive circular dichroism band near 215 nm and a negative band at 225-240 nm, have been proposed to reflect an extended h e l i~.~~?~~ In fact, Wender et al 9 have recently suggested that an extended helix may be the conformation of thexrosslinking areas of elastin since it would allow the formation of intramolecular condensations of lysine pairs.…”

A structural model for desmosine cross-linked peptides

“…Circular-dichroism studies suggest that desmosine-enriched peptides, although enriched in alanine, are in an extended helix rather than an a-helix (Foster et al, 1976). Although the extended helix differs slightly from an a-helix, the separation of the lysine residues does not seem too distant for condensation of cross-link intermediates (Wender et al, 1974).…”