Protease-resistant compounds useful as shuttles through the blood-brain barrier and shuttle-cargo constructs

US9475840B2 · kind B2 · utility

Assignees

• UNIVERSITAT DE BARCELONA · ES
• FUNDACIO INSTITUT DE RECERCA BIOMEDICA (IRB BARCELONA) · ES

Inventors

• Ernest Giralt Lledó · Barcelona, ES
• Meritxell Teixidó Turà · Sant Joan Despí, ES
• Roger Prades Cosano · Barcelona, ES

Key dates

• Filing date: Feb 27, 2013
• Grant date: Oct 25, 2016
• Expiry date: May 18, 2033

Classification

• Technology area (CPC A): Human Necessities
• CPC primary: A61K49/1866
• WIPO field: Pharmaceuticals
• WIPO sector: Chemistry

Abstract

The peptides of formula (I) where: R1 is the group attached to the N-terminal of the first amino acid of the sequence P, optionally via the ligand X, and is selected from H, CH3C(═O)—, and maleimide; X is a biradical selected from —NH—(CH2)r—C(═O)—, —C(═O)—(CH2)r—C(═O)—, —S(CH2)r—, —S—(CH2)r—C(═O)—, —O—(CH2)r—, —S—CH—CH(NH2)—C(═O)—, —O—(CH2)r—C(═O)—, —(CH2)r—C(═O)—, —NH—O—CH2—C(═O)—NH—(CH2)r—CH(NH2)—C(═O)—, —(CH2)r—C(═O)—NH—(CH2)r—CH(NH2)—C(═O)—, and —NH—(CH2)r—CH(NHC(═O)CH2NH2)—C(═O)—; r is 1-5; P is a biradical of an amino acid sequence comprising the sequence D-Pro-D-Trp-D-Val-D-Pro-D-Ser-D-Trp-D-Met-D-Pro-D-Pro-D-Arg-D-His-D-Thr (SEQ ID NO: 1); Y is the group attached to the C-terminal of the last amino acid of the sequence P, and is selected from —NH2, —OH, —OR2 and —NHR2; R2 is a radical selected from (C1-C6)-alkyl and (CH2)2—NH—C(═O)—CH2—O—NH2; k is 0-2; m is 0-1; with the proviso that when the biradical X is —C(═O)(CH2)r—C(═O)—, then R1 is H; when the N of the amino acid of the sequence P to which is attached the biradical X is a biradical —NH—, then m is 1, and when is a biradical —N—, then m is 0; and when R1 is maleimide then the biradical X is —C(═O)—(CH2)r—C(═O)—, —(CH…