APOPTOTISCH WIRKSAME PEPTIDE

摘要

#CMT# #/CMT# Apoptotically active substances (I) include at least one peptide that comprises any of 19 sequences reproduced. #CMT# : #/CMT# Apoptotically active substances (I) include at least one peptide that comprises any of sequences (1)-(19): Arg-Ala-Tyr-Val-Val-Met (1) Arg-Trp-Tyr-Val-Val-Met (2) Arg-Tyr-Tyr-Val-Val-Met (3) Arg-Glu-Tyr-Val-Val-Met (4) Lys-Arg-Ala-Tyr-Val-Val-Met-Trp-Lys-Lys (5) Lys-Arg-Glu-Tyr-Val-Val-Met-Trp-Lys-Lys (6) Arg-Gly-Tyr-Val-Val-Met (7) Arg-Met-Tyr-Val-Val-Met (8) Arg-Thr-Tyr-Val-Val-Met (9) Arg-Asn-Tyr-Val-Val-Met (10) Arg-Asp-Tyr-Val-Val-Met (11) Met-Val-Val-Tyr-Phe-Arg (12) Arg-Ala-Tyr-Val-Val-Ala (13) Arg-Leu-Tyr-Val-Val-Met (14) Arg-Pro-Tyr-Val-Val-Met (15) Arg-Ser-Tyr-Val-Val-Met (16) Arg-Cys-Tyr-Val-Val-Met (17) Met-Val-Val-Tyr-Phe-Arg (18) Met-Val-Val-Tyr-Ala-Arg (19); where (18) and (19) are all-D peptides. #CMT#ACTIVITY : #/CMT# Antiarteriosclerotic; Nootropic; Neuroprotective; Vulnerary; Cytostatic. #CMT#MECHANISM OF ACTION : #/CMT# TSP-1 Dependent Induction of Apoptosis Inhibitor; Apoptosis Inducer. Human umbilical vein endothelial cells, grown to confluence, were incubated with 1 Microg/ml TSP-1 (apoptosis inducer) and 1 mM of various peptides and after 24 hours, they were fixed, stained with DAPI and examined morphologically under a fluorescence microscope or by flow cytometry. For an untreated control, the apoptosis index was 3.28%, compared with 0.38% in presence of peptide (1) and 14.6% in presence of (8), i.e. inhibition index of 75.3% for (1) and -345.1% for (8). #CMT#USE : #/CMT# (I), which may induce or inhibit apoptosis, are useful for treating arteriosclerosis, Alzheimer's disease, wounds, and cancers. When labeled, they are also useful as diagnostic reagents, particularly for detecting arteriosclerotic lesions and cancer. #CMT#BIOLOGY : #/CMT# Preferred Materials: (I) is a protein or peptide, particularly (1)-(19) or their peptidomimetics (e.g. compounds with improved bioavailability and/or metabolic stability, provided by replacing L-amino acids with D-amino acids; altering side chains; altering/extending the main peptide change; cyclization; use of templates to enforce a particular secondary structure, and incorporation of non-peptide components). Peptides (1)-(11) are antiapoptotic while (12)-(19) induce apoptosis. #CMT#ORGANIC CHEMISTRY : #/CMT# Preparation: Peptides are prepared, especially as a library of hexamers by standard chemical synthesis, then screened for their effect on TSP-1 induced apoptosis in human umbilical vein endothelial cells. #CMT#ADMINISTRATION : #/CMT# (I) are administered by injection or inhalation, rectally, topically or orally. #CMT#EXAMPLE : #/CMT# No relevant examples are given in the source material.