A novel anti-HIV synthetic peptide, T-22 ([Tyr5,12,Lys7]-polyphemusin II)

Masuda, Masao; Nakashima, Hideki; Ueda, Toshihiro; Naba, Hiroyasu; Ikoma, Rie; Otaka, Akira; Terakawa, Yoshihiro; Tamamura, Hirokazu; Ibuka, Toshiro; Murakami, Tsutomu; Koyanagi, Yoshio; Waki, Michinori; Matsumoto, Aki; Yamamoto, Naoki; Funakoshi, Susumu; Fujii, Nobutaka

doi:10.1016/0006-291x(92)92280-b

Cited by 120 publications

(52 citation statements)

References 13 publications

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“…These observations suggest that chemokines or chemokine derivatives or small-molecule chemokine receptor antagonists or agonists may be useful for the treatment of HIV-1 infection. Indeed, several groups of low molecular weight compounds are reported to inhibit HIV-1 infection, including the bicyclam AMD3100 (12)(13)(14) and 18-mer peptide T22 (15,16), which potently block HIV-1 entry and infection through CXCR4. More recently, a nonpeptide small molecular weight compound named TAK-779 was found to be a potent and selective CCR5 antagonist (17).…”

mentioning

confidence: 99%

A duodenally absorbable CXC chemokine receptor 4 antagonist, KRH-1636, exhibits a potent and selective anti-HIV-1 activity

Ichiyama

Yokoyama-Kumakura

Tanaka

et al. 2003

Proc. Natl. Acad. Sci. U.S.A.

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150

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confidence: 99%

A duodenally absorbable CXC chemokine receptor 4 antagonist, KRH-1636, exhibits a potent and selective anti-HIV-1 activity

Ichiyama

Yokoyama-Kumakura

Tanaka

et al. 2003

Proc. Natl. Acad. Sci. U.S.A.

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150

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“…Certain AMPs have been shown to inhibit the replication of enveloped viruses such as influenza A virus [32], vesicular stomatitis virus (VSV) and human immunodeficiency virus (HIV-1) [33,34]. The generally accepted mechanism of antiviral action is a direct interaction of these peptides with the envelope of the virus, leading to permeation of the envelope and, eventually, lysis of the virus particle, analogous to the pore-formation model suggested for antibacterial activity.…”

mentioning

confidence: 99%

Antimicrobial peptides: an overview of a promising class of therapeutics

Giuliani¹,

Pirri²,

Nicoletto³

2007

Open Life Sciences

441

459

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Antibiotic resistance is increasing at a rate that far exceeds the pace of new development of drugs. Antimicrobial peptides, both synthetic and from natural sources, have raised interest as pathogens become resistant against conventional antibiotics. Indeed, one of the major strengths of this class of molecules is their ability to kill multidrug-resistant bacteria. Antimicrobial peptides are relatively small (6 to 100 aminoacids), amphipathic molecules of variable length, sequence and structure with activity against a wide range of microorganisms including bacteria, protozoa, yeast, fungi, viruses and even tumor cells. They usually act through relatively non-specific mechanisms resulting in membranolytic activity but they can also stimulate the innate immune response. Several peptides have already entered pre-clinical and clinical trials for the treatment of catheter site infections, cystic fibrosis, acne, wound healing and patients undergoing stem cell transplantation. We review the advantages of these molecules in clinical applications, their disadvantages including their low in vivo stability, high costs of production and the strategies for their discovery and optimization.

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“…For the SAR study in position 3, we therefore replaced 2-Nal with aromatic and aliphatic residues of different size and shape, giving a compound series that contained 50 small (4-6), medium (7)(8)(9)(10), and large (11, 12) side chains (Fig. 2).…”

Section: Design and Sar For Positionmentioning

confidence: 99%

“…7 The majority of the reported peptide antagonists has been developed by Fujii and co-workers, starting from the 18-mer synthetic polyphemusin II analogue T22. 8 Extensive structureactivity relationship (SAR) and downsizing studies first led to the 35 potent 14-mer antagonist T140 (1, Fig. 1), 9 and eventually to the discovery of the cyclopentapeptide FC131 (2, Fig.…”

Section: Introductionmentioning

confidence: 99%

Structure–activity relationship studies of the aromatic positions in cyclopentapeptide CXCR4 antagonists

et al. 2013

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The cyclopentapeptide CXCR4 antagonist FC131 (cyclo(-Arg 1 -Arg 2 -2-Nal 3 -Gly 4 -D-Tyr 5 -), 2; 2-Nal = 3-(2-naphthyl)alanine) represents an excellent starting point for development of novel drug-like ligands with therapeutic potential in HIV, cancer, stem-cell mobilization, inflammation, and autoimmune diseases. While the structure-activity relationships for Arg 1 , Arg 2 , and Gly 4 are well established, less is 10 understood about the roles of the aromatic residues 2-Nal 3 and D-Tyr 5 . Here we report further structureactivity relationship studies of these two positions, which showed that (i) the distal aromatic ring of the 2-Nal 3 side chain is required in order to maintain high potency, and (ii) replacement of D-Tyr 5 with conformationally constrained analogues results in significantly reduced activity. However, a simplified analogue that contained Gly instead of D-Tyr 5 was only 13-fold less potent than 2, which means that the 15 D-Tyr 5 side chain is dispensable. These findings were rationalized based on molecular docking, and the collective structure-activity data for the cyclopentapeptides suggest that appropriately designed Arg 2 -2-Nal 3 dipeptidomimetics have potential as CXCR4 antagonists.

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A novel anti-HIV synthetic peptide, T-22 ([Tyr5,12,Lys7]-polyphemusin II)

Cited by 120 publications

References 13 publications

A duodenally absorbable CXC chemokine receptor 4 antagonist, KRH-1636, exhibits a potent and selective anti-HIV-1 activity

A duodenally absorbable CXC chemokine receptor 4 antagonist, KRH-1636, exhibits a potent and selective anti-HIV-1 activity

Antimicrobial peptides: an overview of a promising class of therapeutics

Structure–activity relationship studies of the aromatic positions in cyclopentapeptide CXCR4 antagonists

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