The overall goal of this program is to elucidate the structural features of antibiotics in the vancomycin class which lead to their ability to complex specifically with certain peptides involved in the biosynthesis of bacterial cell walls. As the first step in the project, the structures of ristocetin A, actinoidins A and B and several other members of the vancomycin group will be determined, looking both at the peptide and the carbohydrate portions. Second, a study will be made of the structural specificities of all the available antibiotics of this group which have defined structures and also certain derivatives of them. These studies will employ Ac2-Lys-D-Ala-D-Ala and related peptides having one or more of the residues replaced by other amino acids. Binding constants will be obtained by UV measurements. Details of binding of the antibiotics with the peptides will be determined by NMR spectroscopy. Finally, after ascertaining the minimum structural features of the antibiotics that are needed to obtain specific peptide binding, new compounds of this type will be prepared and tested for binding and antibiotic activity. In some cases, semisynthetic compounds will be prepared by altering the structures of existing antibiotics, in others they will be prepared de novo taking advantage of a biomimetic synthetic route. By this rational approach to antibiotic design it may be possible to prepare compounds with substantially improved activity.