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Synthetic peptides that inhibit leukocyte superoxide anion production and/or attract leukocytes

a technology of synthetic peptides and superoxide anion, which is applied in the direction of peptides, peptide/protein ingredients, peptide sources, etc., can solve the problems of reperfusion injury, significant tissue injury, morbidity and mortality in humans and animals

Inactive Publication Date: 2004-03-04
BLECHA FRANK +1
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Benefits of technology

These peptides demonstrate antibacterial activity, enhance bacterial susceptibility to phagocytosis, and reduce tissue damage by regulating oxidative responses, providing a dual mechanism to combat infections and promote wound healing.

Problems solved by technology

Infectious diseases are a primary cause of morbidity and mortality in humans and animals.
Although O.sub.2.sup.- and other reactive oxygen intermediates are important components of host defense, these highly toxic oxidants also cause significant tissue injury in inflammatory diseases and ischemia-reperfusion injury (Shasby et al., 1982; Malech, 1987; Demling, 1990; Martinez-Cayuela, 1995; Granger et al., 1995).

Method used

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  • Synthetic peptides that inhibit leukocyte superoxide anion production and/or attract leukocytes
  • Synthetic peptides that inhibit leukocyte superoxide anion production and/or attract leukocytes
  • Synthetic peptides that inhibit leukocyte superoxide anion production and/or attract leukocytes

Examples

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Embodiment Construction

Materials and Methods

[0044] Peptide design and synthesis. Theoretical predictions of peptide characteristics, relative to hydrophilicity, hydrophobicity, and antigenicity, were accomplished using a computer software program (Peptide Companion, Peptide International, Louisville, Ky.). The following peptides were synthesized: PR-39, PR-26, PR-23, PR-19, PR-16, PR-15, and PR-14; the sequences of these peptides appear in the Sequence Listing as Sequence ID Nos. 1 through 7, respectively. Peptides were synthesized by the solid-phase method using t-Boc chemistry with an Applied Biosystems Model 431 Peptide Synthesizer (ABI, Foster City, Calif.). Amino acid derivatives having the L-configuration were used. Peptide purification and characterization were conducted as described previously (Shi et al., 1994b; Shi et al., 1996). Briefly, the peptides were purified on a reversed-phase high-performance liquid chromatography (RP-HPLC) system (Beckman Instruments, Fullerton, Calif.) with a Vydac 21...

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Abstract

Methods of inhibiting leukocyte O2<-> production and attracting leuckocytes using specific peptides are disclosed. These peptides include the proline-arginine (PR)-rich antimicrobial peptide known as PR-39 and truncated analogs thereof. These peptides can be used as medicaments that fight infection by attracting leukocytes to a wound site, yet restrict tissue damage at the wound site caused by excessive oxygen radicals produced by these leukocytes.

Description

[0001] This is a continuation of application Ser. No. 08 / 930,777 filed Oct. 8, 1997, which is a 35 U.S.C. 371 application of PCT / US96 / 04674 filed Apr. 10, 1996, which is a continuation-in-part of application Ser. No. 08 / 419,066 filed Apr. 10, 1995, now U.S. Pat. No. 5,830,993, which are incorporated by reference herein.SEQUENCE LISTING[0003] A Sequence Listing containing 9 sequences in the form of a computer readable ASCII file in connection with the present invention was filed in application Ser. No. 08 / 930,777. This earlier filed CRF is incorporated herein by reference and applicant requests that this previously filed CRF be used as the CRF for this application. A paper copy of this sequence is included herein and is identical to this previously-filed CRF.[0004] 1. Field of the Invention[0005] The present invention is broadly concerned with methods of inhibiting leukocyte superoxide anion (O.sub.2.sup.-) production and methods of attracting a leukocyte to a location using peptides...

Claims

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Application Information

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Patent Type & Authority Applications(United States)
IPC IPC(8): A61K38/00A61K38/08A61K38/17C07K14/00C07K14/47
CPCA61K38/08C07K14/4705A61K38/1709C07K7/06C07K7/08
Inventor BLECHA, FRANKSHI, JISHU
Owner BLECHA FRANK