Three New Cryptophycins from<i>Nostoc</i>sp. GSV 224

Subbaraju, Gottumukkala V.; Golakoti, Trimurtulu; Patterson, Gregory M. L.; Moore, Richard E.

doi:10.1021/np960700a

Cited by 80 publications

(58 citation statements)

References 4 publications

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“…GSV 224. [61][62][63][64] The major naturally occurring representative of this class of cyclic depsipeptides, cryptophycin 1 (Figure 4), shows excellent activity against a broad spectrum of solid tumors, including drug-resistant ones, implanted in mice. 61,65,66 Structure-activity relationship (SAR) studies have shown that an intact 16-membered peptolide ring is essential for optimal cytotoxicity.…”

Section: ␤ 2 Hala Derivatives As Part Of Peptidesmentioning

confidence: 99%

β²‐amino acids—syntheses, occurrence in natural products, and components of β‐peptides^1,2

2004

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Although they are less abundant than their alpha-analogues, beta-amino acids occur in nature both in free form and bound to peptides. Oligomers composed exclusively of beta-amino acids (so-called beta-peptides) might be the most thoroughly investigated peptidomimetics. Beside the facts that they are stable to metabolism, exhibit slow microbial degradation, and are inherently stable to proteases and peptidases, they fold into well-ordered secondary structures consisting of helices, turns, and sheets. In this respect, the most intriguing effects have been observed when beta2-amino acids are present in the beta-peptide backbone. This review gives an overview of the occurrence and importance of beta2-amino acids in nature, placing emphasis on the metabolic pathways of beta-aminoisobutyric acid (beta-Aib) and the appearance of beta2-amino acids as secondary metabolites or as components of more complex natural products, such as peptides, depsipeptides, lactones, and alkaloids. In addition, a compilation of the syntheses of both achiral and chiral beta2-amino acids is presented. While there are numerous routes to achiral beta2-amino acids, their EPC synthesis is currently the subject of many investigations. These include the diastereoselective alkylation and Mannich-type reactions of cyclic- or acyclic beta-homoglycine derivatives containing chiral auxiliaries, the Curtius degradation, the employment of transition-metal catalyzed reactions such as enantioselective hydrogenations, reductions, C-H insertions, and Michael-type additions, and the resolution of rac. beta2-amino acids, as well as several miscellaneous methods. In the last part of the review, the importance of beta2-amino acids in the formation of beta-peptide secondary structures is discussed.

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Section: ␤ 2 Hala Derivatives As Part Of Peptidesmentioning

confidence: 99%

β²‐amino acids—syntheses, occurrence in natural products, and components of β‐peptides^1,2

2004

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“…GSV 224 by Moore and co-workers. 11,12 Cryptophycin-1 (Cr-1, 1, Fig. 1), the major constituent of several other closely related macrolides, demonstrated potent cytotoxicity.…”

Section: T H E C R Y P T O P H Y C I N Smentioning

confidence: 99%

“…2). 1,12,19 Of these, Cr-1 (1) was the major isolate (220 mg, from 50 g of lyophilized alga) and had the most potent cytotoxicity. Cryptophycin-21 (12), the natural product without the C6 methyl substituent on the b-amino acid component was the next most abundant material (14 mg from 50 g of alga).…”

Section: T H E N a T U R A L P R O D U C T Smentioning

confidence: 99%

The cryptophycins: Their synthesis and anticancer activity

Eggen¹,

Georg

2002

Medicinal Research Reviews

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The cryptophycins are a unique family of 16-membered macrolide antimitotic agents isolated from the cyanobacteria Nostoc sp. Their molecular target is tubulin protein wherein they are the most potent known stabilizers of microtubule dynamics and depolymerize microtubules at higher concentrations. They also deactivate the Bcl2 protein and produce apoptotic response much more quickly and at considerably lower concentrations than clinically utilized compounds. The presence of several amide and ester linkages within the cryptophycin core provides access to very convergent total synthetic approaches. Likewise, the modularity of the structure renders their synthesis amenable to structure-activity studies in several regions of the molecule. The in vivo hydrolytic instability of the C5 ester was a key obstacle to the successful identification of a clinical candidate. This problem was ameliorated by increased substitution at C6 as in the presence of gem-dimethyl substitution in the clinical candidate, cryptophycin-52.

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“…2 ' 3 " ,16 or Arenastatin A Although relatively little is known about the interactions of cryptophycins with tubulin, it is believed that the cryptophycins may interact in a manner different from those of other tubulin-binding antimitotic agents. 7 -1 9 For the development of these promising compounds into useful chemotherapeutic a ents, detailed information about the binding domain of the cryptophycins is essential. 0 Hence, we planned to prepare analogues with affinity labels at the two aromatic rings of the cryptophycin molecule.…”

Section: Introductionmentioning

confidence: 99%

Synthesis of Cryptophycin Affinity Labels and Tubulin Labeling

Yang¹,

Georg²

2005

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Three New Cryptophycins fromNostocsp. GSV 224

Cited by 80 publications

References 4 publications

β²‐amino acids—syntheses, occurrence in natural products, and components of β‐peptides^1,2

β²‐amino acids—syntheses, occurrence in natural products, and components of β‐peptides^1,2

The cryptophycins: Their synthesis and anticancer activity

Synthesis of Cryptophycin Affinity Labels and Tubulin Labeling

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Three New Cryptophycins fromNostocsp. GSV 224

Cited by 80 publications

References 4 publications

β2‐amino acids—syntheses, occurrence in natural products, and components of β‐peptides1,2

β2‐amino acids—syntheses, occurrence in natural products, and components of β‐peptides1,2

The cryptophycins: Their synthesis and anticancer activity

Synthesis of Cryptophycin Affinity Labels and Tubulin Labeling

Contact Info

Product

Resources

About

β²‐amino acids—syntheses, occurrence in natural products, and components of β‐peptides^1,2

β²‐amino acids—syntheses, occurrence in natural products, and components of β‐peptides^1,2