Antineoplastic agents. 251. Isolation and structure of stylostatin 1 from the Papua New Guinea marine sponge Stylotella aurantium

Pettit, George R.; Srirangam, Jayaram K.; Herald, Delbert L.; Erickson, Karen L.; Doubek, Dennis L.; Schmidt, Jean M.; Tackett, Larry P.; Bakus, Gerald J.

doi:10.1021/jo00052a041

Cited by 62 publications

(39 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Notably, Diez et al measured a value of 9 ppm for Δδ β,γ of c(NSLAIPF), 20 which indicated a cis conformation of the Ile-Pro amide bond, in agreement with the reported X-ray structure. 21 In this previous work, they also reported that an increase of the proportion of DMSO decreases the cis/trans conformational ratio in constrained derivatives of c(NSLAIPF), as a solvent-induced isomerization effect, 34 which is in line with the present findings that the trans conformer dominates over the cis conformer in pure DMSO; though in water, the cis conformer might be the more populated one, as in the case of c(NSLAIPF). The structural analysis of the trans conformer showed NOE correlations 35 not only between vicinal residues, but also between NH protons of the pairs Ser-Ile, Thr-Ile and Ala-Ser (green circles in Figure 4 and Table S1).…”

Section: Nmr Study Of C(kstaipf)supporting

confidence: 88%

“…All the other conformers of the cyclopeptides were built from the initial models of cis c(NSLAIPF) and trans c(KSTAIPF) (see Experimental Section and Figure S7). First of all, it is important to mention that simulated cis c(NSLAIPF) reproduces all the structural features of the reported X-ray structure 21 Figure 5). 40 Moreover, the Ile carbonyl group was oriented towards the exterior of the molecule, in agreement with the cis Ile-Pro conformation.…”

Section: Molecular Dynamics Of Monomeric Cis and Trans Conformers Of supporting

confidence: 55%

“…22 Both NMR and X-ray analysis showed that stylostatin 1 is found in a cis Ile-Pro conformation, which is stabilized by three internal hydrogen bonds. 20,21 However, inclusion of the lactam dipeptide yielded pseudostylostatins that adopted both cis and trans conformations. Although the turn centred on the Ser-Leu dipeptide was successfully mimicked by the piperidone surrogate, it induced the destabilization of the internal hydrogen bonds found in stylostatin 1, and the increased flexibility allowed for the onset of the Ile-Pro trans conformation.…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Proline cis–trans isomerization and its implications for the dimerization of analogues of cyclopeptide stylostatin 1: a combined computational and experimental study

López-Martínez

Flores-Morales

Cruz

et al. 2016

Phys. Chem. Chem. Phys.

View full text Add to dashboard Cite

dCis and trans proline conformers are often associated with dramatic changes in the biological function of peptides. A slow equilibrium between cis and trans Ile-Pro amide bond conformers occurs in constrained derivatives of the native marine cyclic heptapeptide stylostatin 1 (cyclo-(NSLAIPF)); a potential anticancer agent. In this work, four cyclopeptides, cyclo-(NSTAIPF), cyclo-(KSTAIPF), cyclo-(RSTAIPF) and cyclo-(DSTAIPF), which are structurally related to stylostatin 1, are experimentally and computationally examined in order to assess the effect of residue mutations on the cis-trans conformational ratio and the apparent capacity to form dimeric aggregates. Primarily, cyclo-(KSTAIPF) and cyclo-(RSTAIPF) showed specific trends in circular dichroism, MALDI-TOF and HPLC purification experiments which suggests the occurrence of peptide dimerization. Meanwhile, NMR spectrum of cyclo- (KSTAIPF) indicates that this cyclopeptide exists in the two slow-exchange families of conformations mentioned above. Molecular dynamics simulations combined with quantum mechanical calculations have shed light on the factors governing the cis/trans conformational ratio. In particular, we have found that residue mutations affect the internal hydrogen bond pattern which ultimately tunes the cis/trans conformational ratio and that only trans conformers are capable of aggregating due to the shape complementarity of the two subunits.

show abstract

Section: Nmr Study Of C(kstaipf)supporting

confidence: 88%

Section: Molecular Dynamics Of Monomeric Cis and Trans Conformers Of supporting

confidence: 55%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Proline cis–trans isomerization and its implications for the dimerization of analogues of cyclopeptide stylostatin 1: a combined computational and experimental study

López-Martínez

Flores-Morales

Cruz

et al. 2016

Phys. Chem. Chem. Phys.

View full text Add to dashboard Cite

show abstract

“…We describe here the isolation and structure Considerable research effort is currently being focused on determination of these two novel alkaloids as well as their sigdiscovery of new marine animal antineoplastic and (or) cytonificant cancer cell growth inhibitory activity. toxic constituents based on nitrogen, oxygen, and (or) sulfur heterocyclic systems (2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15). Among the nitrogen heterocyclic compounds, dolastatins 10 (16) (1) and 15 (17) (2), ecteinascidin 729 (9) (3), and cephalostatin 1 (4) (18) are especially noteworthy.…”

Section: Introductionmentioning

confidence: 99%

Antineoplastic agents 285. Isolation and structures of cephalostatins 14 and 15

Pettit

Ichihara

et al. 1994

Can. J. Chem.

Self Cite

View full text Add to dashboard Cite

,2260 (1994).The tube-inhabiting marine worm, Cephalodiscus gilchristi has been found to produce a series of cytotoxic and antineoplastic disteroidal alkaloids. A substantial study concerned with discovery of new cell growth inhibitory constituents of this marine animal has led to isolation of cephalostatins 14 (50) and 15 (5b). The structures were determined by interpretation of spectral data, principally high-field (400 and 500 MHz) NMR and HRFABMS combined with NMR spectral relationships to cephalostatin 1 (4) where the structure was previously assigned by X-ray crystal structure analysis. The stereochemical assignments were established employing the ROESY NMR technique. Both new cephalostatins significantly inhibited growth of the P388 lymphocytic leukemia and a selection of human cancer cell lines. The two new cephalostatins further enhance knowledge of structure-activity parameters for these potentially important steroidal alkaloids. On a trouvC que le ver marin habitant un tube, Cephalodiscus gilchristi, produit une sCrie d'alcaloi'des distCroi'daux cytotoxiques et antinCoplastiques. Une Ctude importante relative B la dCcouverte de nouveaux constituants de cet animal marin inhibants la croissance de nouvelles cellules a conduit B I'isolement des cephalostatines 14 (50) et 15 (5b). On a dCtermini le structures par I'interprCtation des donnCes spectrales obtenues principalement par RMN A champ ClevC (400 et 500 MHz) et par HRFABMS combink avec des relations spectrales avec la ctphalostatine 1 (4) dont la structure a Cte attribuCe anterieurernent par diffraction des rayons X. Les attributions stCrkochimiques ont Ct C faites par la technique REOSY de la RMN. Les deux nouvelles cCphalostatines inhibent fortement la croissance de la leuctmie lymphocytaire P388 ainsi qu'une selection de cellules humaines can&reuses. Les deux nouvelles ~Cphalostatines augmentent nos connaissances sur les paramktres structure-activitC de ces alcaloi'des stCroi'daux potentiellement importants.[Traduit par la ridaction]

show abstract

“…Their biological properties range from neurotoxicity, immunosuppression, antiviral and antifungal activity to cytotoxicity [1]. During the last years, a large number of cytostatic cyclic peptides, like hymenistatin 1 [2], stylostatin [3] and the groups of patellamides, lissoclinamides [4] and axinastatins [5], were isolated from marine sponges and other marine animals all over the world. Recently, two new members of the phakellistatin group [6], the cyclic heptapeptides phakellistatin 2 from the ocean marine sponge Phakellia carteri [7] and phakellistatin 4 from Phakellia costata [8], were isolated by Pettit and co-workers in 10-4% and 10-5% yields (Fig.…”

Section: Introductionmentioning

confidence: 99%