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Modified leptin polypeptides and their uses

一种瘦素、修饰基的技术,应用在瘦素多肽领域,能够解决不具特异性、活性丧失、缺乏再现性等问题

Inactive Publication Date: 2011-01-05
AMBRX
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Some derivatives are too slow to be used in practice
Some derivatives cause loss of protein activity due to attachment to sites responsible for protein activity
Some derivatives are not specific in the site to which they will be attached, which may also lead to loss of desired activity and lack of reproducibility of results

Method used

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  • Modified leptin polypeptides and their uses
  • Modified leptin polypeptides and their uses
  • Modified leptin polypeptides and their uses

Examples

Experimental program
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specific Embodiment approach

[0214] I. Introduction

[0215] The present invention provides leptin molecules comprising at least one unnatural amino acid. In certain embodiments of the invention, the leptin polypeptide having at least one unnatural amino acid includes at least one post-translational modification. In one embodiment, said at least one post-translational modification comprises reacting a molecule comprising a second reactive group with at least one molecule comprising a first reactive group using chemistry known to those skilled in the art to be applicable to a particular reactive group. Molecules containing a second reactive group include (but are not limited to): labels, dyes, polymers, water-soluble polymers, derivatives of polyethylene glycol, photocrosslinking agents, cytotoxic compounds, drugs, affinity tags, photoaffinity tags, reactive compounds, resins, second proteins or polypeptides or polypeptide analogs, antibodies or antibody fragments, metal chelators, cofactors, fatty acids,...

example

[0717] The following examples are provided to illustrate, but not limit, the claimed invention.

example 1

[0719] This example describes one of many possible sets of criteria for selecting preferred sites in hGH for incorporation of non-naturally encoded amino acids.

[0720] This example illustrates how to select preferred sites within hGH polypeptides for the introduction of non-naturally encoded amino acids. The crystal structure 3HHR consisting of hGH in complex with two molecules of the extracellular domain of the receptor (hGHbp) was used to determine preferred locations where one or more non-naturally encoded amino acids may be introduced. Other hGH structures (eg 1AXI) were used to examine possible variations in primary and secondary structural elements between crystal structure datasets. Coordinates for these structures are available from the Protein Data Bank (PDB) (Bernstein et al., J. Mol. Biol. 1997, 112, p. 535) or via the Structural Bioinformatics Research Consortium, available on the World Wide Web at rcsb.org Laboratory PDB (The Research Collaboratory for Structur...

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Abstract

Modified human teptin polypeptides and uses thereof arc provided.

Description

[0001] Cross References to Related Applications [0002] This application claims priority and rights to U.S. Provisional Patent Application No. 61 / 027,414, filed February 8, 2008, and U.S. Provisional Patent Application No. 61 / 112,671, filed November 7, 2008, each of The specification and disclosure are incorporated herein in their entirety. technical field [0003] The present invention relates to leptin polypeptides modified with at least one non-naturally encoded amino acid. Background technique [0004] The obese (ob) gene product, leptin, is an important circulating signal in body weight regulation (Zhang Y et al. (1994) Nature 372:425-432). Mice homozygous for the nonfunctional ob gene become morbidly obese and diabetic due to overfeeding and increased metabolic efficiency. In 1995, Tartaglia L A et al. (Cell 83:1263-1271) described a high affinity receptor (OB-R) for murine leptin. There are indications that the weight reducing effects of leptin may be mediated th...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C12P21/00C07K14/00C07H21/04
CPCC07K14/5759A61P15/00A61P3/04A61P43/00A61P3/10
Inventor 瓦迪姆·克赖诺夫安娜玛莉亚·A··海斯·蒲楠尼克·克努森杰森·品克史塔夫希瑟·马拉洛林·沙利文
Owner AMBRX
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