| Since known enzymatic and chemical methods for sequencing from the C-terminus fail to provide the generality and sensitivity of the Edman degradation, we propose an approach to C-terminal sequencing based on esterification of the carboxy terminus with an alcohol bearing ligating atoms which will have an affinity for low-valent transition metals. Achieving our goal of C-terminal sequencing requires chemospecific binding of a metal to the C-terminus of a protein, with a metal-protein ratio of 1:1. Subsequent oxidative addition of the ester C-O bond to the metal anchors the metal firmly at the C-terminus. The oxidative addition chemistry of alkyl and amino acid esters was studied. 2-((diphenylphosphino)methyl)quinolin-8-ol was synthesized from 2-methylquinolin-8-ol by protection, lithiation, phosphinylation, and deprotection. The corresponding acetate ester reacts with the rhodium (I) dimer, ;Long polypeptides are either enzymatically or chemically cleaved into small fragments to be sequenced by the Edman degradation. There is a need for reagents with more specificity which would permit cleavage of amide bonds in the vicinity of aromatic residues, phenylalanine, tyrosine, or tryptophan. Novel 5 ruthenium cyclopentadiene complexes of the general formula ;Upon addition of external ligands such as trimethylphosphine and N, N-dimethylhydrazine, the bound acetyl amide becomes uncoordinated. Chiral amino acids of N-acetyl-(L)-phenylalanine also react with the Rh(I) in a 1:1 ratio, yielding two products in a ratio of 4:1. The CbzGlyGly ester of 2-... |
