Indolicidin analogs and methods of using same

Details Indolicidin analogs and methods of using same Indolicidin analogs and methods of using same

A - Human Necessities

61

K

A61K 38/16 (2006.01) C07H 21/04 (2006.01) C07K 7/08 (2006.01) A61K 38/00 (2006.01)

Patent

CA 2325659

The present invention relates to 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-NH2 ("Indol 1-13;" SEQ ID NO: 1). The indolicidin analogs of the invention include, for example, analogs such as Indol 2-13 (SEQ ID NO: 2) and Indol 3-13 (SEQ ID NO: 3), which are truncated at the amino terminus by one and two amino acids, respectively, as compared to Indol 1-13 (SEQ ID NO: 1); analogs in which at least one Trp residue in an amino terminal truncated indolicidin analog is replaced by a Phe residue ("Indol/F" analogs); indolicidin analogs comprising, at the carboxy terminus, a homoserine residue; and fusion polypeptides comprising an indolicidin analog. In addition, the invention provides nucleic acid molecules encoding the indolicidin analogs of the invention or precursors of such analogs. The invention also relates to methods of using the indolicidin analogs to reduce or inhibit microbial growth or survival by contacting an environment capable of sustaining microbial growth with the indolicidin analog.

L'invention concerne des analogues d'indolicidine, l'indolicidine est un peptide existant à l'état naturel présentant la séquence d'acides aminés Ile-Leu-Pro-Trp-Lys-Trp-Pro-Trp-Trp-Pro-Trp-Arg-Arg-NH¿2? ("Indol 1-13"; SEQ ID NO: 1). Les analogues d'indolicidine contiennent par exemple des analogues tels que l'Indol 2-13 (SEQ ID NO: 1) et l'Indol 3-13 (SEQ ID NO: 3) qui sont tronqués à l'extrémité N-terminale par un ou deux acides aminés, respectivement, en comparaison avec l'Indol 1-13 SEQ ID NO: 1); des analogues dans lesquels au moins un reste de Trp se trouve dans un analogue d'indolicidine tronqué à l'extrémité N-terminale est remplacé par un reste de Phe ("Indol/F" analogues); des analogues d'indolicidine comprenant au niveau C-terminal un reste d'homosérine; et des polypeptides hybrides contenant un analogue d'indolicidine. L'invention concerne en outre des molécules d'acide nucléique codant pour les analogues d'indolicidine ou les précurseurs de ces analogues. L'invention concerne également les procédés d'utilisation des analogues d'indolicidne afin de réduire ou d'inhiber la croissance ou survie microbienne en mettant en contact un environnement capable d'assurer la croissance microbienne avec l'analogue d'indolicidine.

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