RESUMO
The water accessibilities to aspartyl residues at positions 7 and 23 in the amyloid beta 1-28 peptide associated with Alzheimer's Disease have been calculated using different techniques. These accessibilities of water were compared to those of the succinimidyl residues (SUC) replacing the aspartyl ones (ASP). It has been possible to ascertain that these modifications (ASP--->SUC) lead to a significant increase in the water accessibility to the backbone and alpha-carbon atom of the SUC7 and SUC23 residues. It is suggested that the spontaneous transformation of the ASP--->SUC might lead to an increase of the racemization rates due to the higher accessibility of water at these sites. It is also proposed that the behavior of the adjacent residues in the selectivity of the racemization is to control the water accessibility at the reactive residue.
Assuntos
Peptídeos beta-Amiloides/química , Ácido Aspártico , Fragmentos de Peptídeos/química , Succinimidas , Sequência de Aminoácidos , Modelos Moleculares , Ressonância Magnética Nuclear Biomolecular , Conformação Proteica , Solubilidade , SolventesRESUMO
By computer simulations--molecular mechanics and molecular dynamics with the amber force field (Weiner et al, (1986), J. Comp. Chem. 7, 230-252)--we have determined the stabilities of oligoribotide strands built with D- and L-riboses, and of peptide chains with D- and L-amino acid residues. In particular, complementary double-chains of oligoribotides were studied, since they are an important feature of the growing mechanism of modern nucleic acids. Peptide chains on the other hand, grow without need of a template. We found that mixed oligoribotides are less stable than homochiral ones, and that this chiral effect is less noticeable in peptide chains. The results support the interpretation that L-riboses act as terminators to the template-assisted growth of oligo-r-GD (enantiometric cross-inhibition; Joyce et al., (1987), Proc. Natl. Acad. Sci. USA 84, 4398-4402). Based on this effect, a chemical pathway is proposed which could, under assumed prebiotic conditions, bypass the hindrance of homochiral growth.