Brop: A new reagent for coupling N-methylated amino acids

Coste, J. H.; Dufour, Marie-Noëlle; Pantaloni, A.; Castro, Bertrand

doi:10.1016/s0040-4039(00)94598-2

Cited by 96 publications

(50 citation statements)

References 15 publications

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“…Even better in the presence of a completely derivatized (2) in Scheme 1, is the use of a water soluble carbodiimide EDC [1-ethyl-3-(3 -dimethylaminopropyl) carbodiimide hydrochloride] [35], whose urea can be washed out by aqueous extraction [36]. A worthy successor to the conventional azide coupling has been the use of DPPA (5) [37], and PyBrop (6) [38]. So together with these newer coupling agents and those listed in Table 1, anyone contemplating a macrocyclization step at present has a wide choice of reagents.…”

Section: Cyclization Of Homodetic Peptides (All-amide Linked)mentioning

confidence: 99%

The cyclization of peptides and depsipeptides

Davies

2003

Journal of Peptide Science

416

241

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Constricting the peptide backbone into a more defined conformational form through cyclization is an activity evolved in nature and in synthetic work, the latter straddling only the most recent decades. The resulting conformational constraints increase the probability of an optimum response with bio-receptors. The purpose of this review is to highlight developments that have proved to be reasonably efficient in the macrocyclization of linear precursors into cyclic peptides and depsipeptides.

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Section: Cyclization Of Homodetic Peptides (All-amide Linked)mentioning

confidence: 99%

The cyclization of peptides and depsipeptides

Davies

2003

Journal of Peptide Science

416

241

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“…By contrast, the caged derivative 8 is inactive as a chymotrypsin substrate (Figure 2). As in the case of the caged SH2 ligand 4, increasing photolysis times converts increasing amounts of caged analogue (8) to the active substrate (7). To the best of our knowledge, compound 8 is the first example of a caged proteinase sensor.…”

mentioning

confidence: 97%

“…9 These domains bind to phosphorylated Tyr-(pTyr) containing residues positioned within an appropriate amino acid sequence context on a peptide or protein. 8 For example, the Lck SH2 domain displays a moderate affinity (K D ≈ 1-5 μM) for peptides of the general form Ac-pTyr-Xaa-Xaa-Ile-amide (Figure 1). Previous structural studies have reported that the amide moiety linking the pTyr-Xaa dyad forms a key hydrogen bond with the SH2 domain.…”

mentioning

confidence: 99%

Photochemically-Activated Probes of Protein−Protein Interactions

2007

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The activity of light-activatable ("caged") compounds can be temporally and spatially controlled, thereby providing a means to interrogate intracellular biochemical pathways as a function of time and space. Nearly all caged peptides contain photocleavable groups positioned on the side chains of key residues. We describe an alternative active site targeted strategy that disrupts the interaction between the protein target (SH2 domain, kinase, and proteinase) and a critical amide NH moiety of the peptide probe.Living cells have been referred to as the test tubes of the 21st century. 1 Indeed, a host of reagents have been described for inhibiting, manipulating, or visualizing a wide variety of intracellularly relevant processes. Nonetheless, key challenges remain before the cell-as-atest-tube analogy can be fully realized. A particularly confounding attribute that differentiates living cell biochemistry from its counterpart in the test tube is that the cell, not the investigator, controls where and when a given transformation occurs. Light-activatable ("caged") compounds allow the investigator to retain control over the activity of the bioreagent, even after it has entered the cell. 2 In this regard, a number of caged derivatives of small molecules, including ATP, glutamate, NO, and many others, has been described.2c Furthermore, recent interest in defining the temporal and spatial dynamics of signaling pathways, biochemical cascades largely driven by protein-protein interactions, has led to the construction of caged peptide derivatives.3 The latter compounds are designed to engage specific protein recognition motifs, but only upon photoactivation. Several examples of peptide-based protein kinase sensors3e,g and inhibitors3b as well as 14-3-33d and SH23c,f domain-targeting species have been reported. The general strategy for the preparation of these peptidic species is based on the side-chain modification (with photolabile groups) of key residues required for biorecognition, such as Ser or Tyr for protein kinases or phosphorylated Ser or Tyr for 14-3-3 and SH2 domains, respectively. Unfortunately, many amino acids lack side chain functionality necessary for modification whereas the preparation of caged derivatives of those that can be modified is typically a multistep, off-resin, process.Protein-protein interactions are often dependent upon one or a few key amino acid residues. These residues must be able to achieve the requisite contacts with the protein-binding partner in order for recognition and/or catalysis to occur. In many instances, the amide NH of the essential and/or adjacent residue is crucial for proper orientation of the critical side chain. We reasoned that the incorporation of a photolabile moiety on this key amide nitrogen could significantly compromise recognition or catalysis, via loss of amide hydrogen bond donating ability and/or the presence of a sterically demanding light-cleavable substituent. This notion has been examined via the design, synthesis, and characterization of caged pepti...

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“…11,12 Phosphorylation solely at the 4"-hydroxyl position was accomplished via the coupling of the 3'-amino stilbene 1a to O-tertbutyl-N α -Z-L-Tyr using PyBroP as the coupling reagent to provide amide 7 (Scheme 2). 28 tert-Butyl removal using TFA in DCM followed by phosphorylation afforded the dibenzyl ester 8. Debenzylation at the ester, and benzyloxycarbonyl removal at the amine, were achieved simultaneously with the in situ generation of trimethylsilyl iodide (TMSI) from the reaction of sodium iodide and chlorotrimethylsilane in acetonitrile.…”

Section: Resultsmentioning

confidence: 99%

Antineoplastic Agents. 515. Synthesis of Human Cancer Cell Growth Inhibitors Derived from 3,4-Methylenedioxy-5,4‘-dimethoxy-3‘-amino-Z-stilbene

et al. 2005

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Further structure-activity relationship (SAR) exploration of 3,4-methylenedioxy-5,4′-dimethoxy-3′-amino-Z-stilbene (1a) derivatives resulted in the efficient synthesis of tyrosine amide hydrochloride 9, two tyrosine amide phosphate prodrugs (3a and 6), and sodium aspartate amide 11. Two additional cancer cell growth inhibitors (14 and 16) were synthesized by employing peptide coupling between amine 1a and the Dap residue of dolastatin 10 (4a) to yield amide 14 followed by to yield peptide 16. The latter represents a combination of stilbene 1a with the des-Doe tetrapeptide unit of the powerful tubulin assembly inhibitor dolastatin 10. Peptide 16 was examined for potential binding to tubulin in the vinca and/or colchicine regions and found to perform primarily as a relative of dolastatin 10. Amide 14 had anticryptococcal and antibacterial activities.We recently completed syntheses of 3'-amino derivatives (1a-b, 1d-j) of combretastatin A-2 (2c) 1 , encouraged by the remarkable success of the potent cancer vascular targeting [2][3][4] that occurs with combretastatin A-4 phosphate prodrug (CA4P) 2h. [5][6][7][8][9][10] Subsequently, we undertook the synthesis and initial anticancer evaluation of two phosphate derivatives (3a,b) of tyrosine stilbene amide 1i. Attachment of the phosphate group at the 3'-phenol position has been investigated in detail in the combretastatin A and B series. 1,[11][12][13] In the present study we chose to use the 4"-hydroxyl group of tyrosine amide 1i for attachment of a phosphate group (3a) as well as obtaining a diphosphoryl derivative (3b) by phosphorylating tyrosine amide 1i at both the amine 14 and hydroxyl groups. A parallel important objective of this research involved employing a tetrapeptide segment of dolastatin 10 (4a) for bonding to the 3′-amino group (1b). Dolastatin 10 (D-10, 4a), isolated 15-17 from the Indian Ocean sea hare Dolabella auricularia, has continued to progress through preclinical 18 and clinical development as an impressive antineoplastic agent. [19][20][21][22] Dolastatin 10 (4a) and various synthetic derivatives also have specific antifungal activity against Cryptococcus neoformans. 23,24 Previous SAR studies have confirmed that D-10 (4a) inhibits microtubule assembly by binding to the β-tubulin subunit near the vinca site. SAR studies have shown the des-Doe tetrapeptide unit (4b, Dov-Val-Dil-Dap) to be necessary for potent anticancer * To whom correspondence should be addressed. bpettit@asu 25,26 We now also report synthesis of the amide representing coupling of amine 1a to Dov-Val-Dil-Dap (4b). Results and DiscussionOur synthesis of the tyrosine stilbene amide 1i 27 presented the opportunity to develop two additional phosphate prodrugs in the combretastatin series. Accordingly, the 4"-phenol and α-amino groups were phosphorylated in one step using dibenzyl phosphite (1i to 5) (Scheme 1). Debenzylation of the resulting phosphate diesters (5) was achieved using bromotrimethylsilane to afford the free acid (3b) which was subsequently converted to sod...

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Brop: A new reagent for coupling N-methylated amino acids

Cited by 96 publications

References 15 publications

The cyclization of peptides and depsipeptides

The cyclization of peptides and depsipeptides

Photochemically-Activated Probes of Protein−Protein Interactions

Antineoplastic Agents. 515. Synthesis of Human Cancer Cell Growth Inhibitors Derived from 3,4-Methylenedioxy-5,4‘-dimethoxy-3‘-amino-Z-stilbene

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