A dozen years of retro-inverso peptidomimetics

Chorev, Michael; Goodman, Murray

doi:10.1021/ar00029a007

Cited by 221 publications

(166 citation statements)

References 70 publications

(24 reference statements)

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“…Indeed, several groups have observed that retroenantiomeric peptides may display comparable biological activities as the parent peptides (Chorev and Goodman, 1993). In line with this, the structural evaluation of a cyclic Fcε RI α-chain-derived peptide and its retro-inverso motif by NMR showed similarity of the surface topology of both compounds (McDonnell et al, 1997).…”

Section: Other Cyclic Upa-derived Peptide Variantsmentioning

confidence: 63%

Cyclo19,31[D-Cys19]-uPA19-31 Is a Potent Competitive Antagonist of the Interaction of Urokinase-Type Plasminogen Activator with Its Receptor (CD87)

Magdolen

Bürgle²,

Na³

et al. 2001

Biological Chemistry

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IntroductionThe serine proteases urokinase-type plasminogen activator (uPA) and plasmin, in concert with other proteolytic enzymes (e. g. matrix metalloproteases, cysteine proteases), are involved in tumor-associated processes such as cell invasion and regulation of cell/cell and cell/matrix contacts Schmitt et al., 2000;Andreasen et al., 2000). (pro-)uPA binds to a specific, high-affinity cell surface receptor, uPAR (CD87), which is composed of three structurally homologous, independently folded domains (Dear and Medcalf, 1998). In addition, there are also cellular binding sites for plasmin(ogen) (Félez, 1998). In consequence, binding of (pro-) uPA to cell membrane-anchored uPAR significantly increases plasmin generation due to a distinct increase of reciprocal activation of pro-uPA and plasminogen (Ellis et al., 1991). Plasmin not only degrades a variety of components of the extracellular matrix (e. g. fibrin and laminin), but also activates certain matrix metalloproteases (in addition to pro-uPA) which break down additional structural proteins of the extracellular matrix such as various collagens. Thus, cell surface-triggered plasminogen activation plays a fundamental role in tissue remodeling, which is a prerequisite for tumor cell invasion and metastasis Schmitt et al., 2000;Andreasen et al., 2000).The interaction of pro-uPA or its activated form high molecular weight (HMW-)uPA with uPAR has been characterised in detail. Although the N-terminal domain I of uPAR contains major determinants for uPA-binding, high affinity interaction with uPA is dependent on the multidomain structure of the receptor, indicating that all three protein domains are involved in the formation of a composite ligand binding site (Ploug, 1998;Gårdsvoll et al., 1999;Bdeir et al., 2000). In contrast, uPA binds to uPAR via a defined continuous peptide sequence

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Section: Other Cyclic Upa-derived Peptide Variantsmentioning

confidence: 63%

Cyclo19,31[D-Cys19]-uPA19-31 Is a Potent Competitive Antagonist of the Interaction of Urokinase-Type Plasminogen Activator with Its Receptor (CD87)

Magdolen

Bürgle²,

Na³

et al. 2001

Biological Chemistry

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“…[15][16][17][18] Since the retro-inverso modification leads to similar topographies, differing primarily by the reversed direction of amide bonds, it is a useful approach to elucidate the role of direction of the peptide backbone in molecular recognition. Ligands 1 (or 2) and 3 (or 4) are partial retro-inverso isomers where the structures are same in the opioid region but different in the CCK region (Figure 1).…”

Section: Introductionmentioning

confidence: 99%

Partial Retro−Inverso, Retro, and Inverso Modifications of Hydrazide Linked Bifunctional Peptides for Opioid and Cholecystokinin (CCK) Receptors

et al. 2006

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Partially modified retro-inverso, retro, and inverso isomers of hydrazide linked bifunctional peptides were designed, synthesized, and evaluated for bioactivities at δ/μ opioid receptors and CCK-1/CCK-2 receptors. All modifications of the CCK pharmacophore moiety affected bioactivities for the CCK-1 and CCK-2 receptors (up to 180-fold increase in the binding affinity with higher selectivity) and for the δ and μ opioid receptors. The results indicate that the opioid and CCK pharmacophores in one molecule interact with each other to induce topographical changes for both pharmacophores.

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“…To this end we introduced an ethylene bridge between the of the N i , from the reversed peptide bond (C i O-N iϩ1 H3 N i H-C iϩ1 O), and the original N iϩ3 forming a [1,4,7]triazecane-3,8,10-trione ring system that replaces the C i O ⅐ ⅐ ⅐ HN iϩ3 10-membered hydrogenbonded ring of a classical ␤-turn ( Figure 13). 68 The novel N i -to-N iϩ3 -ethylene-bridged partially modified RI tetrapeptide ␤-turn mimetic (EBRIT-BTM) was synthesized efficiently from the fully protected N,NЈ- …”

Section: Variations On the Themementioning

confidence: 99%

“…Jointly we explored the synthetic routes for the construction of retro-inverso (RI) peptide bonds in linear peptides, sorted their stereochemical and conformational properties, analyzed this structural transformation conceptually, monitored its development by others, and periodically summarized the state of the art in reviews and opinion articles. [2][3][4][5][6] During this adventure, we formulated new concepts, tested new hypotheses, and spent many hours in heated discussions in Murray's office, around the pool in La Jolla, over the phone, through the Internet, and at various meeting points around the globe. We shared the delight and satisfaction of seeing new insights and applications generated by others as the RI modification spread to laboratories around the world in many cases leading to fascinating findings.…”

Section: Introductionmentioning

confidence: 99%