The Rockefeller University

Riso National Laboratory

Research, Incorporated

Robert B Merrifield

James P Tam

Cecilia G Unson

Rolf Henrik Berg

Hans G Boman

Arne Holm

Kristoffer Almdal

Walther B Pedersen

David Andreu

David Wade

Tai W Wong

William F Heath, Jr

The invention relates to antibacterial and antimalarial peptides which are hybrids peptides which a of naturally occurring peptides such as cecropins, attacins, magainins, sarcotoxin, sapecin, bactenecins, alamethidicins, defensins and PGLa, and toxins such as streptolysins, melittin, barbatolysin, paradaxins and delta hemolysin. The hybrid peptides of the present invention are easily synthesized and have reduced toxicity. Also included in the invention are pharmaceutical compositions containing such hybrid peptides, and methods of treating patients infected with an organism against which these peptides are active.

Antibacterial and antimalarial hybrid peptides

Glucagon analogs characterized principally by substitution of amino acid residues at positions 9, 11, 16, and 21 with or without a histidine residue at the amino terminus are useful adjuncts to insulin therapy.

Glucagon analogs with serine replacements

Antibiotically and/or antimalarially active D-peptides of naturally occurring antibiotics such as cecropin A, B and D, melittin, and Magainin I and II and their addition, deletion and replacement analogs including homologous and heterologous analogs thereof.

Antibiotic peptides containing D-amino acids

Glucagon analogs characterized principally by the removal or replacement of the 9-aspartic acid residue or its replacement with another amino acid residue together with replacement of the 16-serine residue and possible replacement of the 11-serine residue and 21-aspartic acid residue with or without a histidine at the amino terminal are useful adjuncts to insulin therapy.

A method for the solid-phase synthesis of peptides or proteins in high yield and high purity uses a solid support consisting of a functionalized polystyrene-grafted polymer substrate, the grafted polystyrene chains being substantially non-cross-linked and having a chain molecular weight, not including optional non-reactive substituents, of at least 200,000, preferably in the range of 600,000-1,200,000. Particularly suitable polymer substrates are substrates of a polyolefin such as polyethylene. The method is particularly well-suited to the compartmentalized synthesis of a multitude of peptides or proteins in a parallel and substantially simultaneous fashion. Preferred embodiments of a solid support for performing the synthesis are prepared from thin polyethylene sheet or film which has been grafted with polystyrene chains in a radical-initiated process in which the polyethylene sheet or film is immersed in a solution of optionally substituted styrene monomer in an alcohol such as methanol, the volume percentage of styrene in the solution preferably being about 30% v/v, and subjected to gamma irradiation.

Peptide synthesis method and solid support for use in the method

A method for the solid-phase synthesis of peptides or proteins in high yield and high purity uses a solid-support consisting of a functionalized polystyrene-grafted polymer substrate, the grafted polystyrene chains being substantially non-cross-linked and having a chain molecular weight, not including optional non-reactive substituents, of at least 200,000, preferably in the range of 600,000-1,200,000. Particularly suitable polymer substrates are substrates of a polyolefin such as polyethylene. The method is particularly well-suited to the compartmentalized synthesis of a multitude of peptides or proteins in a parallel and substantially simultaneous fashion. Preferred embodiments of a solid support for performing the synthesis are prepared from thin polyethylene sheet or film which has been grafted with polystyrene chains in a radical-initiated process in which the polyethylene sheet or film is immersed in a solution of optionally substituted styrene monomer in an alcohol such as methanol, the volume percentage of styrene in the solution preferably being about 30% v/v, and subjected to gamma irradiation.

Glucagon analogs characterized principally by the removal of the 9-aspartic acid residue or its replacement with an amino acid residue other than an L- dibasic amino acid containing up to five carbon atoms with or without a histidine at the amino terminal are useful adjuncts to insulin therapy.

Glucagon analogs with ASP.sup.9 replacements or deletions

Glucagon analogs characterized principally by deletion of the number one histidine and replacement of the number nine aspartic acid with glutamic acid are useful adjuncts to insulin therapy.

Glucagon homologs and therapeutic use thereof

The preparation of N.sup..alpha. -desacetylthymosin.alpha..sub.1 and its use as a hormonally active agent participating in the regulation, differentiation and function of thymic dependent lymphocytes (T-cells) is described.

N.sup..alpha. -desacetylthymosin.alpha..sub.1 and process

A method of releasing a functional group present in an amino acid or amino acyl residue from a resin or protecting residue which is bonded to the functional group by a linkage having proton affinity, which comprises: reacting the functional group bonded to the organic residue, with a mixture of HF and a base for a time and under conditions effective to produce the release; wherein the amounts of HF and base in the mixture are adjusted so that said release occurs substantially by an S.sub.N 2 mechanism.

Growing community of inventors

Creskill, NJ, United States of America

Robert B Merrifield