Homochiral oligopeptides via a lattice-controlled polymerisation in racemic crystals of valine N-carboxyanhydride suspended in aqueous solutions.
As part of our program on the biochirogenesis of homochiral peptides, we report the formation of racemic parallel (p) beta sheets composed of alternating R and S chains of up to 14-15 repeat units of the same handedness through the polymerisation of (R,S)-valine N-carboxyanhydride (NCA) crystals suspended in aqueous solutions of a primary amine as the initiator. The occurrence of such a lattice-controlled reaction accompanied by a reduction in volume implies the operation of a mechanism that differs from that of the common solid-state polymerisation in vinyl systems. The topotacticity of the reaction is explained through the operation of a multistep nonlinear process comprising lattice control coupled with an asymmetric induction in the formation of homochiral short peptides followed by their self-assembly into racemic p beta sheets, which operate as efficient templates in the ensuing process of enantioselective chain elongation at the polymer/crystal interface. The composition of the diastereoisomeric libraries of oligopeptides was determined by MALDI-TOF and MALDI-TOF-TOF MS analyses of the products obtained from monomers enantioselectively labelled with deuterium. The structure of the p beta sheets could be determined by initiating the polymerisation reaction with water-soluble esters of enantiopure alpha-amino acids or short peptides. The same reaction performed with the monomer crystals suspended in hexane yielded a complex mixture of diastereoisomeric oligopeptides, thus highlighting the indispensable role played by water in controlling the stereoselectivity of the reaction. By contrast, polymerisation of (R,S)-leucine NCA crystals, with a different packing arrangement that presumably does not endorse the formation of periodic peptide templates, yielded, both in aqueous and hexane suspensions, libraries of peptides dominated by heterochiral diastereoisomers.
Eliash
Ran
R
Department of Materials and Interfaces, The Weizmann Institute of Science, 76100 Rehovot, Israel.
Nery
Jose G
JG
Rubinstein
Irena
I
Clodic
Gilles
G
Bolbach
Gérard
G
Weissbuch
Isabelle
I
Lahav
Meir
M
D002082:Butylamines / Q000737:chemistry; D018360:Crystallography, X-Ray; D004952:Esters / Q000737:chemistry; D006586:Hexanes / Q000737:chemistry; D008958:Models, Molecular; D015394:Molecular Structure; D009842:Oligopeptides / Q000737:chemistry*; D012996:Solutions; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D013237:Stereoisomerism; D053719:Tandem Mass Spectrometry; D014633:Valine / Q000031:analogs & derivatives / Q000737:chemistry*
D002082:Butylamines; D004952:Esters; D006586:Hexanes; D009842:Oligopeptides; D012996:Solutions; C030046:N-carboxyvaline anhydride; D014633:Valine; C032462:n-butylamine