The partial retro–inverso modification: A road traveled together

Chorev, Michael

doi:10.1002/bip.20219

Cited by 74 publications

(48 citation statements)

References 72 publications

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“…1 Important classes of molecules studied include neurotransmitters, hormones, inhibitors of proteases and protein kinases, sweeteners, antimicrobial peptides, adhesion molecules, antigenic epitopes, immunomodulators and immunological probes. 2 A large number of molecules have been synthesized by two approaches.…”

mentioning

confidence: 99%

Synthesis of retro-inverso peptides employing isocyanates of Nα-Fmoc-amino acids/peptide acids catalyzed by DMAP

Venkataramanarao

Sureshbabu

2006

Tetrahedron Letters

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mentioning

confidence: 99%

Synthesis of retro-inverso peptides employing isocyanates of Nα-Fmoc-amino acids/peptide acids catalyzed by DMAP

Venkataramanarao

Sureshbabu

2006

Tetrahedron Letters

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“…In the design of peptidomimetics, we used a method known as amino acid retro-inversion (26,27), which consists of the reversal of the peptide backbone stereochemistry (i.e., substitution of Damino acids for the normal L-amino acids) in conjunction with chain reversal. The resulting product is a "retro-inverso" peptidomimetic in which the side-chain topology is similar to the parent peptide (Fig.…”

Section: Resultsmentioning

confidence: 99%

From combinatorial peptide selection to drug prototype (I): Targeting the vascular endothelial growth factor receptor pathway

Giordano

Cardó-Vila

Salameh

et al. 2010

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

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Inhibition of blood vessel formation is a viable therapeutic approach in angiogenesis-dependent diseases. We previously used a combinatorial screening on vascular endothelial growth factor (VEGF)-activated endothelial cells to select the sequence CPQPRPLC and showed that the motif Arg-Pro-Leu targets VEGF receptor-1 and neuropilin-1. Here, we evaluated and validated D (LPR), a derivative molecule with strong antiangiogenesis attributes. This prototype drug markedly inhibits neovascularization in three mouse models: Matrigel-based assay, functional human/murine blood vessel formation, and retinopathy of prematurity. In addition to its systemic activity, D (LPR) also inhibits retinal angiogenesis when administered in an eye-drop formulation. Finally, in preliminary studies, we have showed targeted drug activity in an experimental tumor-bearing mouse model. These results show that drugs targeting extracellular domains of VEGF receptors are active, affect signal transduction, and have potential for clinical application. On a larger context, this study illustrates the power of ligand-directed selection plus retroinversion for rapid drug discovery and development.peptide | cancer | VEGFR | angiogenesis | retinopathy of prematurity

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“…This is known as an "alanine--scan"; Ala is used because it is non--functionalized and has the same conformational preferences as all non--Gly/Pro residues. 9) Retro--inverso peptides: In a retro--inverso analog, the N--to--C direction and stereochemistry of the parent peptide are simultaneously changed, which has the potential of resulting in a peptide with overall similar topology with respect to side chain orientation; see reference [3] for a review. However, due to the reversed N--to--C direction, the positioning of the backbone amide carbonyl (H--bond acceptor) and NH (H--bond donor) groups relative to the side chains will obviously be different.…”

Section: ) Alanine Scanmentioning

confidence: 99%

“…The cyclopentapeptide antagonists [49] ( Figure 5A) were developed from the macrocyclic 14--mer polypeptide lead compound T140 ( Figure 1A) [40], and the downsizing strategy was based on combining the four pharmacophoric residues of T140 (Arg 2 , 2--Nal 3 A solution structure for FC131 based on 1 H--NMR studies in DMSO was also reported [49]. While the exact spatial orientation of the relatively flexible side chains could not be determined, the reported backbone conformation is consistent with later NMR studies of the bioactive (receptor--bound)…”

Section: Discovery Of the Cyclopentapeptide Cxcr4 Antagonistsmentioning

confidence: 99%

Progress Toward Rationally Designed Small-Molecule Peptide and Peptidomimetic CXCR4 Antagonists

Våbenø

Haug

2015

Future Med. Chem.

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Over the last five years, X--ray structures of CXC chemokine receptor 4 (CXCR4) in complex with three different ligands (the small--molecule antagonist IT1t, the polypeptide antagonist CVX15, and the viral chemokine antagonist vMIP--II) have been released. In addition to the inherent scientific value of these specific X--ray structures, they (i) provide a reliable structural foundation for studies of the molecular interactions between CXCR4 and its key peptide ligands (CXCL12 and HIV--1 gp120); and (ii) serve as valuable templates for further development of small--molecule CXCR4 antagonists with therapeutic potential. We here review recent computational studies of the molecular interactions between CXCR4 and its peptide ligands -based on the X--ray structures of CXCR4 -and the current status of small--molecule peptide and peptidomimetic CXCR4 antagonists. 2) Isostere: In the context of this review, an isostere is defined as any functional group or moiety that is included in a peptide sequence as a replacement of an amide bond.3) Scaffold: The term scaffold is used for rigid (normally cyclic) structures onto which the functional groups of amino acid side chains can be introduced. 4) Structure--based and ligand--based design:In structure--based design, the 3D structure of the target is known and guides the design of active compounds. When the 3D structure of the target is unknown, indirect information has to be used in order to design/optimize compounds that bind to the target. This information is normally obtained through SAR studies and pharmacophore modeling, and the overall approach is known as ligand--based design. 5) 7TM receptors: As signalling via G proteins is a common feature for seven--

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The partial retro–inverso modification: A road traveled together

Cited by 74 publications

References 72 publications

Synthesis of retro-inverso peptides employing isocyanates of Nα-Fmoc-amino acids/peptide acids catalyzed by DMAP

Synthesis of retro-inverso peptides employing isocyanates of Nα-Fmoc-amino acids/peptide acids catalyzed by DMAP

From combinatorial peptide selection to drug prototype (I): Targeting the vascular endothelial growth factor receptor pathway

Progress Toward Rationally Designed Small-Molecule Peptide and Peptidomimetic CXCR4 Antagonists

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