A - Human Necessities – 61 – K
Patent
A - Human Necessities
61
K
A61K 38/07 (2006.01) A61K 38/08 (2006.01) A61K 38/12 (2006.01) C07H 21/00 (2006.01) C07K 4/00 (2006.01) C07K 5/10 (2006.01) C07K 5/12 (2006.01) C07K 7/08 (2006.01) A61K 38/00 (2006.01)
Patent
CA 2335650
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-<u>Trp-Pro-Trp-Trp</u>-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-<u>Cys-Pro-Trp-Cys</u>-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.
L'invention concerne des analogues d'indolicidine stabilisés par réticulation, l'indociline étant un peptide naturel comprenant la séquence d'acides aminés Ile-Leu-Pro-Trp-Lys-Trp-Pro-Trp-Trp-Pro-Trp-Arg-Arg-CONH¿2? ("Indol 1-13"; SEQ ID NO :1). Ces analogues d'indolicidine réticulés ("X-indolicidine") comprennent par exemple des analogues tels qu'Indol 1-13 (w6,9), qui présente la structure Ile-Leu-Pro-Trp-Lys-<u>Trp-Pro-Trp-Trp</u>-Pro-Trp-Arg-Arg-CONH¿2? (SEQ ID NO: 3), et Indol 1-13/6,9C(C6,9), qui présente la structure Ile-Leu-Pro-Trp-Lys-<u>Cys-Pro-Trp-Cys</u>-Pro-Trp-Arg-Arg-CONH¿2? (SEQ ID NO: 4), dans lesquels une liaison réticulée est formée entre le premier et le dernier résidu d'acide aminé souligné. L'invention concerne en outre des molécules d'acide nucléique codant pour ces analogues X-indolicidine, et en particulier pour des précurseurs de ces analogues. L'invention concerne également des procédés consistant à utiliser un analogue de X-indolicidine pour réduire ou inhiber la prolifération ou la survie microbienne en appliquant un analogue de X-indolicidine dans un environnement favorable à une prolifération microbienne.
Osapay Klara
Selsted Michael E.
Smart & Biggar
The Regents Of The University Of California
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