CROSSLINK-STABILIZED INDOLICIDIN ANALOGS

摘要

The present invention relates to crosslink-stabilized analogs of indolicidin, which is a naturally occurring peptide having the amino acid sequence Ile-Leu-Pro-Trp-Lys-Trp-Pro-Trp-Trp-Pro-Trp-Arg-Arg-CONH2 ("Indol 1-13"; SEQ ID NO: 1). The cross-linked indolicidin ("X-indolicidin") analogs of the invention include, for example, analogs such as Indol 1-13(W6,9), which has the structure Ile-Leu-Pro-Trp-Lys-Trp-Pro-Trp-Trp-Pro-Trp-Arg-Arg-CONH2 (SEQ ID NO: 3), and Indol 1-13/6,9C(C6,9), which has the structure Ile-Leu-Pro-Trp-Lys-Cys-Pro-Trp-Cys-Pro-Trp-Arg-Arg-CONH2 (SEQ ID NO: 4), where a crosslink formed between the first and last underlined amino acid residues. In addition, the invention provides nucleic acid molecules encoding the X-indolicidin analogs of the invention, particularly precursors of such analogs. The invention also relates to methods of using an X-indolicidin analog to reduce or inhibit microbial growth or survival by contacting an environment capable of sustaining microbial growth with the X-indolicidin analog.