Polyphor Ltd.

Unversität Zürich

Universitaet Zuerich

Polyphor Ag

Jan Wim Vrijbloed

Daniel Obrecht

Frank Gombert

Christian Ludin

Barbara Romagnoli

Steven J Demarco

Kerstin Moehle

Reshmi Mukherjee

Heiko Henze

John Anthony Robinson

John-Anthony Robinson

Sergio Lociuro

Jürg Zumbrunn

Sergio Locurio

Françoise Jung

Alexander Lederer

Francoise Jung

Odile Sellier

Kerstin Möhle

Shivaprasad Shankaramma

Marc Kessler

Frank Otto Gombert

Steve J Demarco

Reshimi Mukherjee

Jurg Zumbrunn

Juerg Zumbrunn

The template-fixed &#x3b2;-hairpin peptidomimetics Cyclo(-Tyr-His-X-Cys-Ser-Ala-Pro-Dab-Arg-Tyr-Cys-Tyr-Gln-Lys-Pro-Pro), disulfide bond between Cys4 and Cys11, and pharmaceutically acceptable salts thereof, with X being Ala or Tyr, have CXCR4 antagonizing properties and can be used for where cancer is mediated or resulting from CXCR4 receptor activity.

Template-fixed peptidomimetics

The template-fixed &#x3b2;-hairpin peptidomimetics Cyclo(-Tyr-His-Cys-Ser-Ala-Pro-Dab-Arg-Tyr-Cys-Tyr-Gln-Lys--Pro-Pro), disulfide bond between Cys4 and Gysl1, and pharmaceutically acceptable salts thereof, with X being Ala or Tyr, have CXCR4 antagonizing properties and can be used for where cancer is mediated or resulting from CXCR4 receptor activity.

The template-fixed B-hairpin peptidomimetics Cyclo(-Tyr-His-X-Cys-Ser-Ala-Pro-Dab-Arg-Tyr-Cys-Tyr-Gln-Lys--Pro-Pro), disulfide bond between Cys4 and Gys11, and pharmaceutically acceptable salts thereof, with X being Ala or Tyr, have CXCR4 antagonizing properties and can be used for where cancer is mediated or resulting from CXCR4 receptor activity.

Template-fixed &#x3b2;-hairpin peptidomimetics of the general formula (I) wherein Z is a template-fixed chain of 12, 14 or 18 &#x3b1;-amino acid residues which, depending on their positions in the chain (counted starting from the N-terminal amino acid), are Gly, NMeGly, Pro or Pip, or of certain types which, as the remaining symbols in the above formula, are defined in the description and the claims, and salts thereof, have CXCR4 antagonizing properties These &#x3b2;-hairpin peptidomimetics can be manufactured by a process which is based on a mixed solid- and solution phase synthetic strategy.

Template-fixed beta-hairpin peptidomimetics with CXCR4 antagonizing activity

The template-fixed &#x3b2;-hairpin peptidomimetics Cyclo(-Tyr-His-X-Cys-Ser-Ala-Pro-Dab-Arg-Tyr-Cys-Tyr-Gln-Lys-Pro-Pro), disulfide bond between Cys4 and Gys11, and pharmaceutically acceptable salts thereof, with X being Ala or Tyr, have CXCR4 antagonizing properties and can be used for preventing HIV infections in healthy individuals or for slowing and halting viral progression in infected patients; or where Cancer is mediated or resulting from CXCR4 receptor activity; or where immunological diseases are mediated or resulting from CXCR4 receptor activity; or for treating immuno suppression; or, in particular, for stem cell mobilization of peripheral blood stem cells and/or mesenchymal stem cell (MSC) and/or other stem cells which retention depend on the CXCR4-receptor. These &#x3b2;-hairpin peptidomimetics can be manufactured by a process which is based on a mixed solid- and Solution phase synthetic strategy, using methods which are well known to those adequately skilled in peptide chemistry.

Template-fixed &#x3b2;-hairpin peptidomimetics of the general formula (I) wherein Z is a template-fixed chain of 12, 14 or 18 &#x3b1;-amino acid residues which, depending on their positions in the chain (counted starting from the N-terminal amino acid), are Gly, NMeGly, Pro or Pip, or of certain types which, as the remaining symbols in the above formula, are defined in the description and the claims, and salts thereof, have CXCR4 antagonizing properties. These &#x3b2;-hairpin peptidomimetics can be manufactured by a process which is based on a mixed solid- and solution phase synthetic strategy.

A method of screening for template-fixed &#x3b2;-hairpin mimetics and libraries including a plurality of these mimetics is provided. The template-fixed &#x3b2;-hairpin mimetics are of the following general formula:R-Cys-Z-Cys-R&#x2003;&#x2003;Iwherein the two cysteine residues are bridged by a disulfide bond, thereby forming a cyclic peptide; Rand Rare di- or tripeptide moieties of certain types, as defined herein; and Z is a chain of n amino acid residues with n being an integer from 4 to 20 and with each of these n amino acid residues being, independently, derived from any naturally occurring L-&#x3b1;-amino acid.

Template fixed beta-hairpin loop mimetics and their use in phage display

Template-fixed &#x3b2;-hairpin mimetics and libraries including a plurality of these mimetics are provided. The template-fixed &#x3b2;-hairpin mimetics are of the following general formula:R-Cys-Z-Cys-R&#x2003;&#x2003;Iwherein the two cysteine residues are bridged by a disulfide bond, thereby forming a cyclic peptide; Rand Rare di- or tripeptide moieties of certain types, as defined herein; and Z is a chain of n amino acid residues with n being an integer from 4 to 20 and with each of these n amino acid residues being, independently, derived from any naturally occurring L-&#x3b1;-amino acid.

Template fixed &#x3b2;-hairpin loop mimetics and their use in phage display

The template-fixed &#x3b2;-hairpin peptidomimetics Cyclo(-Tyr-His-X-Cys-Ser-Ala-Pro-Dab-Arg-Tyr-Cys-Tyr-Gln-Lys-Pro-Pro), disulfide bond between Cys4 and Cys11, and pharmaceutically acceptable salts thereof, with X being Ala or Tyr, have CXCR4 antagonizing properties and can be used for preventing HIV infections in healthy individuals or for slowing and halting viral progression in infected patients; or where cancer is mediated or resulting from CXCR4 receptor activity; or where immunological diseases are mediated or resulting from CXCR4 receptor activity; or for treating immuno suppression; or for treating inflammation, or, in particular, for stem cell mobilization of peripheral blood stem cells and/or mesenchymal stem cell (MSC) and/or other stem cells which retention depend on the CXCR4-receptor.

Template-fixed &#x3b2;-hairpin mimetics and libraries including a plurality of these mimetics are provided. The template-fixed &#x3b2;-hairpin mimetics are of the following general formula:R-Cys-Z-Cys-R&#x2003;&#x2003;(I)wherein the two cysteine residues are bridged by a disulfide bond, thereby forming a cyclic peptide; Rand Rare di- or tripeptide moieties of certain types, as defined herein; and Z is a chain of n amino acid residues with n being an integer from 4 to 20 and with each of these n amino acid residues being, independently, derived from any naturally occurring L-&#x3b1;-amino acid.

Template-fixed &#x3b2;-hairpin peptidomimetics of the general formula (I), wherein Z is a template-fixed chain of 12 &#x3b1;-amino acid residues which, depending on their positions in the chain (counted starting from the N-terminal amino acid) are Gly or Pro, or of certain types, at least one of these residues being of the type of N-substituted glycines, which types, as the remaining symbols in the above formula, are defined in the description and the claims, and salts thereof, have the property to inhibit the growth of or to kill microorganisms. They can be used as disinfectants for foodstuffs, cosmetics, medicaments or other nutrient-containing materials or as medicaments to treat or prevent infections. These &#x3b2;-hairpin peptidomimetics can be manufactured by processes which are based on a mixed solid- and solution phase synthetic strategy. 

Template-fixed peptidomimetics with antimicrobial activity

Template-fixed &#x3b2;-hairpin peptidomimetics of the General Formula (I); wherein Zand Zare template-fixed chains of 4 and 6 or 5 and 7 &#x3b1;-amino acid residues and salts thereof. They have CXCR4-antagonizing properties and can be used as medicaments. These &#x3b2;-sheet peptidomimetics can be manufactured by a process which is based on a mixed solid- and solution phase synthetic strategy. 

Template-fixed peptidomimetics as medicaments against HIV and cancer

Template-fixed &#x3b2;-hairpin peptidomimetics of the general formula (I) wherein Z is a template-fixed chain of 12, 14 or 18 &#x3b1;-amino acid residues which, depending on their positions in the chain (counted starting from the N-terminal amino acid), are Gly, NMeGly, Pro or Pip, or of certain types which, as the remaining symbols in the above formula, are defined in the description and the claims, and salts thereof, have CXCR4 antagonizing properties. These &#x3b2;-hairpin peptidomimetics can be manufactured by a process which is based on a mixed solid&#x2014;and solution phase synthetic strategy.

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Möhlin, Switzerland

Jan Wim Vrijbloed