Long lasting growth hormone releasing factor derivatives

A growth hormone and release factor technology, which is used in drug combinations, medical preparations with non-active ingredients, and medical preparations containing active ingredients, etc.

Inactive Publication Date: 2010-04-21
常山凯捷健生物药物研发(河北)有限公司
View PDF28 Cites 4 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

A series of GRF peptides are listed as possible candidates for stabilization by the methods disclosed in this application, but none are specifically exemplified in the specification

Method used

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
View more

Image

Smart Image Click on the blue labels to locate them in the text.
Viewing Examples
Smart Image
  • Long lasting growth hormone releasing factor derivatives
  • Long lasting growth hormone releasing factor derivatives
  • Long lasting growth hormone releasing factor derivatives

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0135] Tyr-Ala-Asp-Ala-Ile-Phe-Thr-Asn-Ser-Tyr-Arg-Lys-Val-Leu-Gly-Gln-Leu-Ser-Ala-Arg-Lys-Leu-Leu-Gln-Asp- Ile-Met-Ser-Arg-CONH 2

[0136]Step 1: The synthesis of solid-phase peptides was carried out in the order of 100 μmol. The following protected amino acids were added to the resin: Fmoc-Arg(Pbf)-OH, Fmoc-Ser(tBu)-OH, Fmoc-Met-OH, Fmoc-Ile-OH, Fmoc-Asp(tBu)-OH, Fmoc -Gln(Trt)-OH, Fmoc-Leu-OH, Fmoc-Leu-OH, Fmoc-Lys(Boc)-OH, Fmoc-Arg(Pbf)-OH, Fmoc-Ala-OH, Fmoc-Ser(tBu) -OH, Fmoc-Leu-OH, Fmoc-Gln(Trt)-OH, Fmoc-Gly-OH, Fmoc-Leu-OH, Fmoc-Val-OH, Fmoc-Lys(Boc)-OH, Fmoc-Arg(Pbf )-OH, Fmoc-Tyr(tBu)-OH, Fmoc-Ser(tBu)-OH, Fmoc-Asn(Trt)-OH, Fmoc-Thr(tBu)-OH, Fmoc-Phe-OH, Fmoc-IIe- OH, Fmoc-Ala-OH, Fmoc-Asp(tBu)-OH, Fmoc-Ala-OH, Boc-Tyr(tBu)-OH. They were dissolved into N,N-dimethylformamide (DMF) and, in sequence, using O-benzotriazol-1-yl-N,N,N',N'-tetramethyluronium hexafluorophosphate Salt (HBTU) and diisopropylethylamine (DIEA) activation. Removal of the Fmoc protecting gr...

Embodiment 2

[0139] Long-acting derivatives of the GRF peptide of Example 1

[0140] Tyr-Ala-Asp-Ala-Ile-Phe-Thr-Asn-Ser-Tyr-Arg-Lys-Val-Leu-Gly-Gln-Leu-Ser-Ala-Arg-Lys-Leu-Leu-Gln-Asp- Ile-Met-Ser-Arg-Lys(MPA)-CONH 2

[0141] Step 1: This step was performed as in Example 1 above, except that the first amino acid added to the resin was Fmoc-Lys(Aloc)-OH.

[0142] Step 2: Selective deprotection of the Lys(Aloc) group was carried out manually and by dissolving in 5 mL C 6 h 6 : CHCl 3 (1:1): 2.5% NMM (v:v): 3 equivalents of Pd(PPh) in 5% AcOH (v:v) 3 ) 4 The solution treated resin was complete in 2 hours. Then the resin was washed with CHCl 3 (6x5 mL), 20% AcOH in DCM (6x5 mL), DCM (6x5 mL) and DMF (6x5 mL) washes.

[0143] Step 3: The synthesis is automated again with the addition of 3-maleimidepropionic acid (MPA). Between each coupling, the resin was washed three times with N,N-dimethylformamide (DMF) and isopropanol, respectively.

[0144] Step 4: Derivatives were cleaved from...

Embodiment 3

[0146] Tyr-(D)ala-Asp-Ala-Ile-Phe-Thr-Asn-Ser-Tyr-Arg-Lys-Val-Leu-Gly-Gln-Leu-Ser-Ala-Arg-Lys-Leu-Leu-Gln -Asp-Ile-Met-Ser-Arg-CONH 2

[0147] Step 1: The synthesis of solid-phase peptides was performed on the order of 100 μmole. The following protected amino acids were added to the resin in sequence with the procedure described in Step 1 of Example 1: Fmoc-Arg(Pbf)-OH, Fmoc-Ser(tBu)-OH, Fmoc-MetOH, Fmoc-Ile- OH, Fmoc-Asp(tBu)-OH, Fmoc-Gln(Trt)-OH, Fmoc-Leu-OH, Fmoc-Leu-OH, Fmoc-Lys(Boc)-OH, Fmoc-Arg(Pbf)-OH, Fmoc-Ala-OH, Fmoc-Ser(tBu)-OH, Fmoc-Leu-OH, Fmoc-Gln(Trt)-OH, Fmoc-Gly-OH, Fmoc-Leu-OH, Fmoc-Val-OH, Fmoc- Lys(Boc)-OH, Fmoc-Arg(Pbf)-OH, Fmoc-Tyr(tBu)-OH, Fmoc-Ser(tBu)-OH, Fmoc-Asn(Trt)-OH, Fmoc-Thr(tBu)- OH, Fmoc-Phe-OH, Fmoc-Ile-OH, Fmoc-Ala-OH, Fmoc-Asp(tBu)-OH, Fmoc-(D)ala-OH, Boc-Tyr(tBu)-OH.

[0148] Step 2: The implementation of this step is the same as Step 2 of Example 1.

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to view more

PUM

No PUM Login to view more

Abstract

This invention relates to growth hormone releasing factor (GRF) derivatives. In particular, this invention relates to GRF peptide derivatives having an extended in vivo half-life, for promoting the endogenous production or release of growth hormone in humans and animals.

Description

[0001] This application is a divisional application of Chinese patent application 02804497.5 (corresponding to international application PCT / CA02 / 00123) filed on February 1, 2002, entitled "Long-acting growth hormone releasing factor derivatives". field of invention [0002] The present invention relates to growth hormone releasing factor (GRF) derivatives. In particular, the present invention relates to GRF peptide derivatives having an extended half-life in vivo for promoting the endogenous production or release of growth hormone in humans and animals. Background of the invention [0003] Growth hormone (GH), also called somatotropin, is a protein hormone of about 190 amino acids synthesized and secreted by somatotroph cells of the pituitary gland. It is a major player in the control of growth and metabolism. It is also an important medicinal product for humans and animals. GH production is regulated by a variety of factors, including stress, nutrition, sleep, and GH its...

Claims

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to view more

Application Information

Patent Timeline
no application Login to view more
Patent Type & Authority Applications(China)
IPC IPC(8): C07K14/60C07K19/00A61K38/25A61K47/48A61P5/06A61K38/22A61K38/00A61P5/10
CPCA61K38/00C07K14/60A61P3/00A61P3/04A61P3/12A61P5/06A61P5/10A61P9/04A61P17/02A61P19/00A61P19/10A61P21/00A61P43/00
Inventor 多米尼克·P·布赖顿尼赛布·布杰拉布罗杰·莱杰马丁·罗比塔耶露西·热泰科琳·邦盖
Owner 常山凯捷健生物药物研发(河北)有限公司
Who we serve
  • R&D Engineer
  • R&D Manager
  • IP Professional
Why Eureka
  • Industry Leading Data Capabilities
  • Powerful AI technology
  • Patent DNA Extraction
Social media
Try Eureka
PatSnap group products

Browse by: Latest US Patents, China's latest patents, Technical Efficacy Thesaurus, Application Domain, Technology Topic.

© 2024 PatSnap. All rights reserved.Legal|Privacy policy|Modern Slavery Act Transparency Statement|Sitemap