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Compositions and methods for delivery of glycopeptide antibiotics to medical device surfaces

A technology of peptide composition and medical device, applied in chemical instruments and methods, pharmaceutical formulations, medical science, etc., can solve problems such as urinary tract infection

Inactive Publication Date: 2015-01-07
阿非纳金公司 +1
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Unfortunately, virtually all patients with urinary catheters for 28 days or more develop urinary tract infections

Method used

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  • Compositions and methods for delivery of glycopeptide antibiotics to medical device surfaces

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0047] Phage display technology is commonly used to obtain peptides with binding affinities typically mediated by protein-peptide interactions. Phage display has also been successfully used to obtain peptides with binding affinity for surface materials such as metal or polymer surfaces. However, phage display has not been successfully used to obtain high binding affinity (e.g., by EC50 measured less than <1 mM). Thus, the present examples illustrate various methods of using phage display technology to unexpectedly obtain peptides with binding affinity (including high binding affinity) for glycopeptide antibiotics. Peptides with binding affinity for medical device surfaces were developed using first solid phase screening and phage display technology as previously described, followed by peptide design and peptide synthesis for improved binding properties.

[0048] In contrast to previously described phage selection methods, it was unexpectedly found during the development of t...

Embodiment 2

[0064] In this example, other features of the peptides according to the disclosed subject matter are illustrated.

[0065] Structure-function and binding affinity characterization

[0066] Additional peptides were designed starting from the peptide amino acid sequence SSCLIDMYGVCHNFDGAYDSSR (SEQ ID NO: 1) and expressed in the bacterial expression system described herein to further evaluate structure-function relationships. A truncated peptide comprising the amino acid sequence of SEQ ID NO:9 (STCLIDMYGVCH) was expressed and its binding affinity compared to a glycopeptide antibiotic comprising the peptide of SEQ ID NO:1. A dimer of this truncated peptide (SEQ ID NO: 10; STCLIDMYGVCHSSCLIDMYGVCH) with D replaced by A (SEQ ID NO: 11; STCLIAMYGVCH), D replaced by E (SEQ ID NO: 12; STCLIEMYGVCH) and G replaced by S substitution (SEQ ID NO: 13; STCLIDMYSVCH). The relative binding strength of these and other representative peptides to glycopeptide antibiotics was determined by th...

Embodiment 3

[0078] Although other surface-binding peptides known in the art may be used as components of compositions of the disclosed subject matter coupled to peptides of the disclosed subject matter having glycopeptide antibiotic binding affinity, Table 4 exemplifies the Representative peptides for the binding affinity of the material ("surface-bound peptides"). For example, the surface-binding peptide comprises the following amino acid sequences: SEQ ID NO: 14-35 with binding affinity for polystyrene; SEQ ID NO: 36 with binding affinity for polyurethane; SEQ ID NOs: 37-50 with polycarbonate binding affinity; SEQ ID NOs: 51-56 with polycarbonate binding affinity; SEQ ID NOs: 57-65 with nylon binding affinity; with Teflon binding affinity SEQ ID NOS: 66 and 67; SEQ ID NOS: 68 and 69 with binding affinity for polyethylene terephthalate fibers; SEQ ID NOS: 70 and 71 with binding affinity for collagen-based substrates; SEQ ID NOS: 72-119 having binding affinity for metals (eg, including o...

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PUM

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Abstract

The presently disclosed subject matter relates to peptides having binding affinity for glycopeptide antibiotics and methods and compositions for delivering glycopeptide antibiotic to the surface of medical devices. The peptide compositions can comprise a peptide having binding affinity for a surface material of a medical device that is coupled to the peptide having binding affinity for glycopeptide antibiotic. Also provided are methods of applying the peptide compositions to a medical device by contacting the peptide compositions with a surface of the medical device. In addition, kits are provided comprising the peptide compositions.

Description

[0001] Cross References to Related Applications [0002] The presently disclosed subject matter claims the benefit of U.S. Provisional Patent Application Serial No. 60 / 981,565, filed October 22, 2007, and U.S. Provisional Patent Application Serial No. 61 / 056,746, filed May 28, 2008, each of which discloses Incorporated herein by reference in its entirety. [0003] funding statement [0004] The disclosed subject matter was made in part with government support (Grant No. 1R43DE018584-01 from the National Institute of Dental and Craniofacial Research and Grant No. 9R44AI082540-02 from the National Institute of Allergy and Infectious Diseases). Accordingly, the United States Government has certain rights in the disclosed subject matter. technical field [0005] The disclosed subject matter relates to compositions for the delivery of glycopeptide antibiotics to the surface of medical devices. More particularly, the disclosed subject matter relates to a set of peptides having...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): A61K38/00
CPCA61L29/08A61L27/28C07K2319/00C07K14/001A61L31/047A61L31/16A61L27/227A61L29/16A61L31/08A61L27/54A61L2300/252A61L2300/406C07K7/06C07K7/08A61L29/048
Inventor 马丁·K·达比伊萨克·G·桑福德R·爱德华·本松汉内·格龙保罗·T·哈米尔顿什里库马尔·A·奈尔道格·比希特埃利奥特·格鲁斯金
Owner 阿非纳金公司
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