Ellman J A, Mendel D, Schultz P G
Department of Chemistry, University of California, Berkeley 94720.
Science. 1992 Jan 10;255(5041):197-200. doi: 10.1126/science.1553546.
A number of unnatural amino acids and amino acid analogs with modified backbone structures were substituted for alanine-82 in T4 lysozyme. Replacements included alpha,alpha-disubstituted amino acids, N-alkyl amino acids, and lactic acid, an isoelectronic analog of alanine. The effects of these electronic and structural perturbations on the stability of T4 lysozyme were determined. The relatively broad substrate specificity of the Escherichia coli protein biosynthetic machinery suggests that a wide range of backbone and side-chain substitutions can be introduced, allowing a more precise definition of the factors affecting protein stability.
