Abstract: The invention provides novel macrocyclic peptides and methods for their preparation. The invention also provides pharmaceutical compositions and methods to treat, prevent or ameliorate a cell proliferative disease or conditions. e.g., a cancer. in a subject in need thereof, including but not limited to a colon cancer, such as MSS or MSI colon cancer, and pancreatic cancer. This invention provides for the synthesis and development of novel anticancer agents that are based on the core structure Sansalvamide A (San A).

Abstract: The invention provides a method for making a combinatorial library of cyclic compounds, such as Holliday junction-trapping compounds, comprising the steps of (a) obtaining a plurality of trimers according to the generic structure X1-X2-X3, wherein X1, X2 and X3 can be independently any naturally or nonnaturally occurring amino acids or peptidomimetics thereof; (b) optionally coupling a spacer S to the trimer at either end; (c) cyclizing two trimers or trimer-spacer conjugates in a head-to-tail orientation; thereby obtaining a combinatorial library of compounds, wherein the library does not include an unmodifed or naturally occurring Holliday Junction-trapping compounds. The invention additionally provides methods macrocyclic compounds that are synergimycin derivatives.