Thrombosis Research Institute

Trigen Gmbh

Vijay Vir Kakkar

John Joseph Deadman

Michael Finbarr Scully

Goran Karl Claeson

Naoyashi Chino

Leifeng Cheng

Xinjie Lu

Said Mohamed Elgendy

Geeta Patel

Donovan S Green

Said Mohammed Elgendy

Michael Finbar Scully

Said Mohamed Anwar Elgendy

Christopher Andrew Goodwin

Jehan A Baban

Donovan St Green

Kalwant S Authi

Goran K Claeson

The invention relates to multiple epitope constructs, immunogenic and vaccine compositions comprising recombinant molecules presenting inserted multiple and different epitopes from a variety of antigens. The antigenic determinants being associated with different pathways leading to atherosclerosis. In particular, the invention relates to such compositions for eliciting an immune response against antigens and pathogens involved in the development of atherosclerosis the invention includes intermethods of treating and/or preventing the disease and recombinant protein products.

Multi-epitopic construct

The invention relates to a recombinant protein comprising: a carrier portion; a first epitope capable of eliciting an anti-atheroma response; and a second epitope capable of eliciting an anti-atheroma response, characterized in that said first and second epitopes are distinct from one another.

Anti-atheroma vaccine

Dendroaspin, a polypeptide neurotoxin analogue is modified by recombinant DNA techniques, particularly &ldquo;loop grafting&rdquo; to provide a modified polypeptide. The modified polypeptide is constructed so as to retain dendroaspin activity, for example, platelet adhesion to fibrinogen, in addition to possessing one or more further biological or biochemical activities not native to dendroaspin, for example, platelet derived growth factor (PDGF) activity or hirudin activity.

Bi-or multifunctional molecules based on a dendroaspin scaffold

Peptides which act as inhibitors or substrates of thrombin are provided. The peptides of the invention have the general structural formula:

Inhibitors and substrates of thrombin

Serine protease inhibitors

This invention provides peptides of the formula ##STR1## wherein X is H, CH.sub.3 or an N-protecting group;

Peptides which act as inhibitors or substrates of thrombin are derived from the formula: D-Phe-Pro-Arg or its analogues, wherein Phe is substituted by (a), wherein Ar.sub.1 or Ar.sub.2 are the same or different and are selected from the group consisting of phenyl, thienyl, pyridyl, naphthyl, thionaphtyl, indolyl and saturated groups corresponding to these, optionally substituted by up to three groups selected from C.sub.1 -C.sub.3 alkyl and C.sub.1 -C.sub.3 alkoxy, L.sub.1 and L.sub.2 are the same of different and are selected from the group consisting of CH.sub.2, C.sub.2 --C.sub.2, O-CH.sub.2, S-CH.sub.2, Ar-L taken together optionally means H, diphenyl-methyl, fluorenyl or saturated groups corresponding to these, but one of the Ar-L cannot be H when the other [CH.sub.2 ].sub.n -Q, (c) where Q=H, amino, amidino, imidazole, guanidino or isothioureido and n=1-5, preferably 3-5, or C.sub.3 -C.sub.9 alkyl and C.sub.5 -C.sub.10 aryl or alkylaryl optionally substituted by up to three groups selected from hydroxy and C.sub.1 -C.sub.4 alkoxy; Z=CN, COR.sub.1, (d) or (e), where R.sub.1 =H, OH, CH.sub.2 Cl, CH.sub.2 --C.sub.2 --CO--pip, CF.sub.2 --CF.sub.2 --CO--pip, (f), (g), CH.sub.2 --C.sub.2 --CO--Pro--NHEt, CF.sub.2 --CF.sub.2 --CO--Pro--NHEt or a chromophoric group e.g. pHA, MCA, R.sub.2 and R.sub.3 are the same or different and are selected from the group consisting of OH, OR.sub.6 and NR.sub.6 R.sub.7, or R.sub.2 and R.sub.3 taken together represent the residue of a diol; where R.sub.6 and R.sub.7, which are the same or different, are C.sub.1 -C.sub.10 alkyl, phenyl or C.sub.6 -C.sub.10 arylalkyl, R.sub.4 and R.sub.5 are the same or different and are selected from R.sub.2, R.sub.3, Gly-pip, Ala-pip or Gly-Pro-NHEt.

Stable .alpha.-substituted boronic esters, e.g. for use in peptide synthesis, are prepared by reacting a substituted alkene of the formula: ##STR1## with a disubstituted borane of the formula: ##STR2## wherein: (i) R.sup.1 and R.sup.2 are each selected from various groups which are preferably not leaving groups;

Growing community of inventors

Bickley, United Kingdom

Vijay Vir Kakkar