Bicycle Therapeutics Limited

Amersham Pharmacia Biotech UK Limited

Nycomed Amersham Plc

Other

Medical Research Council

David Loakes

Daniel M Brown

Gregory Paul Winter

Clifford Leslie Smith

Alan L Hamilton

Adrian Christopher Simmonds

Christian Heinis

Elise Bernard

Shiv R Kumar

Mark McDougall

Satyam Nampalli

Marina Vaysburd

Daniel Paul Teufel

Fergal Hill

Lutz Riechmann

John Tite

Jan Balzarini

William Jonathan Cummins

David Williams

Kazuo Negishi

Patrick Finn

Constantin Neagu

Dan Brown

Kei Moriyama

Paul Gregory Winter

John Paul Tite

The invention relates to a method for providing a multispecific peptide ligand comprising a polypeptide covalently linked to a molecular scaffold at three or more amino acid residues and capable of binding to two or more separate targets, comprising the steps of: (a) providing a first repertoire of polypeptides, each polypeptide comprising two or more reactive groups capable of covalent linkage to a molecular scaffold, and at least one loop which comprises a sequence of two or more amino acids subtended between two of said reactive groups; (b) providing a second repertoire of polypeptides as described in (a); (c) joining at least one loop of one or more members of the first repertoire to at least one loop of one or more members of the second repertoire to form at least one polypeptide comprising two loops, and (d) conjugating the composite polypeptide(s) to a molecular scaffold at at least three amino acid positions.

Multispecific peptides

The invention relates to a method for modifying one or more peptide ligands, comprising polypeptides covalently linked to a molecular scaffold at two or more amino acid residues, comprising the steps of providing one or more peptide ligands, wherein the polypeptide comprises two or more reactive groups which form a covalent linkage to the molecular scaffold, and at least one loop which comprises a sequence of two or more amino acids subtended between two of said reactive groups; exposing the peptide ligands to one or more proteases; and sorting the ligands according to the extent of proteolytic cleavage.

Structured peptide processing

The invention relates to a method for altering the conformational diversity of a first repertoire of polypeptide ligands, comprising a plurality of polypeptides comprising at least two reactive groups separated by a loop sequence covalently linked to a molecular scaffold which forms covalent bonds with said reactive groups, to produce a second repertoire of polypeptide ligands, comprising assembling said second repertoire from the polypeptides and structural scaffold of said first repertoire, incorporating one of the following alterations: (a) altering at least one reactive group; or (b) altering the nature of the molecular scaffold; or (c) altering the bond between at least one reactive group and the molecular scaffold; or (d) any combination of (a), (b) or (c).

Peptide libraries

Disclosed is a pharmaceutical composition comprising a ribonucleoside analogue in accordance with general formula I or II as herein defined, in admixture with a physiologically acceptable excipient diluent or carrier.

Inhibition of viruses

Base analogues

Nucleoside analogues or base analogues having structure (I), where X&equals;O or NH or S, Y&equals;N or CHR or CR , W&equals;N or NR or CHR or CR or S, n&equals;1 or 2; each R is independently H or O or alkyl or alkenyl or alkoxy or aryl or a reporter moiety; where necessary (i.e. when Y and/or W is N or CR where R is not O) a double bond is present between Y and W or W and W, and Q is H or a sugar or a sugar analogue or a nucleic acid backbone or backbone analogue.

Nucleoside analogues have structure (2) wherein Q is H or a sugar moiety or sugar analogue or a modified sugar or a nucleic backbone or backbone analogue, W is an alkylene or alkenylene chain of 0-5 carbon atoms, any of which may carry a substituent R , X is O or N or NR or CR , X&prime; is O or S or N, provided that when X&prime; is O or S, then X is C, Y is CH or N, R is NH or SMe or SO Me or NHNH , each of R and R is independently H or F or alkyl or alkenyl or aryl or acyl or a reporter moiety, R is independently H or alkyl or alkenyl or aryl or acyl or a reporter moiety, and R is H or &boxH;O or F or alkyl or aryl or a reporter moiety.

Tricyclic base analogues

Nucleoside analogues containing the degenerate base analogue P and derivatives thereof are provided with reporter moieties preferably comprising signal moieties. The nucleoside analogues are useful for labeling DNA or RNA or for incorporating in oligonucleotides.

Nucleoside analogues

Nucleoside analogues in which a group M replaces the natural base where M is (1) or (2) or (3), where each of X,, X,and X,are C or N, each of R,and R,is the same or different and each is H, NO,, CO, COR,, OR,, CN, O, CON(R,),, COOR,, SO,R,, SO,R,, SR,, NHCHO, (CH,),(R,),, halogen, or a reporter moiety, each of R,and R,is H or hydrocarbyl or a reporter moiety, and n is 0-4. The analogues are substrates for polymerase and terminal transferase enzymes.

Growing community of inventors

Cambridge, United Kingdom

David Loakes