US 6,444,645 B1 · Crosslink-stabilized indolicidin analogs

Abstract

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 crosslinked 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.

Claims17

Dependent claims

A crosslinked indolicidin (X-indolicidin) analog having the amino acid sequence:

Xaa1-Xaa2-Xaa3-Xaa4-Xaa5-Xaa6-Pro-Xaa6-Xaa6-Pro-Xaa5-Xaa7-Xaa7-Xaa5,
wherein:
Xaa1 is Ile, Leu, Val, Ala, Gly or absent;
Xaa2 is Ile, Leu, Val, Ala, Gly or absent;
Xaa3 is Pro or absent;
Xaa4 is Trp, Phe, Cys, Glu, Asp, Lys, AlaL or absent;
Xaa5 is Arg, Lys or absent;
Xaa6 is Trp, Phe, Cys, Glu, Asp, Lys, or AlaL;
Xaa7 is Arg, Lys or absent;
and
Xaa8 is homoserine (Hse), Met, Met-Xaa9-Met or absent;
wherein Xaa9 is one or more amino acids;
provided that a crosslink can be formed between two amino acids selected from the group consisting of:
a) Xaa4, when present, and an Xaa6;
and
b) a first Xaa6 and another Xaa6;
and further provided that:
if Xaa2 is absent, Xaa1 is absent;
if Xaa3 is absent, Xaa1 and Xaa2 are absent;
if Xaa4 is absent, Xaa1, Xaa2 and Xaa3 are absent;
and
if Xaa5 is absent, Xaa1, Xaa2, Xaa3 and Xaa4 are absent,
and wherein said crosslinked indolicidin analog has antimicrobial activity.

20 more elements

Dependencies are inferred from the claim text.

Crosslink-stabilized indolicidin analogs

Life of this patent

Crosslink-stabilized indolicidin analogs

Life of this patent

Abstract

Claims17