4125-98-8

Upstream product

• 74-89-5 methylamine 
• 163887-30-7 N-Z-N-Me-(S,R)-Ile 
• 61548-98-9 C₉H₉NO₂C₂H₃CHC 
• 3160-59-6 N-benzyloxycarbonyl-isoleucine 
• 66866-65-7 3-benzyloxycarbonyl-4-(2-methylpropyl)oxazolidin-5-one 
• 319-78-8 isoleucine 
• 865-47-4 potassium tert-butylate 
• 74-88-4 methyl iodide 
• 2503-13-1 Enniatin-A 
• 105091-14-3 theonellamine B 
• 1047981-71-4 viridamide A 
• 1334149-95-9 apratoxin S₅ 
• 1334149-96-0 apratoxin S₆ 
• 1334149-94-8 apratoxin S₄ 

Downstream Products

• 69941-95-3 N-methyl-N-(2.4-dinitro-phenyl)-L-isoleucine 
• 132385-54-7 5-sec-Butyl-3-[1-(6,7-dimethoxy-quinazolin-4-yl)-piperidin-4-ylmethyl]-1-methyl-2-thioxo-imidazolidin-4-one 
• 138775-22-1 N-Fmoc-N-methyl-L-isoleucine 
• 820972-74-5 N-Nitroso-N-methyl-L-isoleucyl-D-α-hydroxy-isovaleriansaeure-(4-nitro-benzylester) 
• 50673-48-8 N-methyl-D-allo-isoleucine 
• 220663-32-1 <2-C(S)>-Fmoc-NMeIle-Thr(Ψ^H,pmppro)-OBn 
• 220663-33-2 <2-C(R)>-Fmoc-NMeIle-Thr(Ψ^H,pmppro)-OBn 
• 42807-92-1 N-Methyl-isoleucinmethylester 
• 603973-36-0 Fmoc-NMeIle-Thr(Ψ^Me,Mepro)-OBn 

Relevant academic research and scientific papers

Komesuamide and odopenicillatamide, two linear lipopeptides from the marine cyanobacterium Caldora penicillata

The linear lipopeptides komesuamide (1) and odopenicillatamide (2) were isolated from Caldora penicillata a marine cyanobacterium collected in Okinawa. The structures of these compounds were established by spectroscopic analyses, and the absolute configurations were determined by HPLC analyses of the acid hydrolysates. Both compounds showed glucose uptake activity at 40 μM in cultured L6 myotubes.

Iheyamides A-C, Antitrypanosomal Linear Peptides Isolated from a Marine Dapis sp. Cyanobacterium

Iheyamides A (1), B (2), and C (3), new linear peptides, were isolated from a marine Dapis sp. cyanobacterium. Their structures were elucidated by spectroscopic analyses and degradation reactions. Iheyamide A (1) showed moderate antitrypanosomal activities against Trypanosoma brucei rhodesiense and Trypanosoma brucei brucei (IC50 = 1.5 μM), but the other two analogues, iheyamides B (2) and C (3), did not (IC50 > 20 μM, respectively). The structure-activity relationship clarified that an isopropyl-O-Me-pyrrolinone moiety was necessary for the antitrypanosomal activity. Furthermore, the cytotoxicity of 1 against normal human cells, WI-38, was 10 times weaker than its antitrypanosomal activity (IC50 = 18 μM).

Isolation and structure elucidation of cyclopeptide alkaloids from the leaves of Heisteria parvifolia

Heisteria parvifolia Sm. is prescribed in traditional medecine against numerous diseases in C?te d'Ivoire. Due to the shortcoming in scientifical knowledge of use of this species, our investigations revealed five undescribed cyclopeptide alkaloids added to one known derivative namely anorldianine. These compounds were elucidated by 1D and 2D-NMR experiments and comparison with literature data, and confirmed by HR-ESI-MS. Cytotoxic activity evaluation of these compounds against the chronic myeloid leukemia (K565) cell line exhibited an antiproliferative activity with cell growth inhibition from 13% to 46%.

Discovery of new A- and B-type laxaphycins with synergistic anticancer activity

Two new cyclic lipopeptides termed laxaphycins B4 (1) and A2 (2) were discovered from a collection of the marine cyanobacterium Hormothamnion enteromorphoides, along with the known compound laxaphycin A. The planar structures were solved based on a combined interpretation of 1D and 2D NMR data and mass spectral data. The absolute configurations of the subunits were determined by chiral LC-MS analysis of the hydrolysates, advanced Marfey's analysis and 1D and 2D ROESY experiments. Consistent with similar findings on other laxaphycin A- and B-type peptides, laxaphycin B4 (1) showed antiproliferative effects against human colon cancer HCT116 cells with IC50 of 1.7 μM, while laxaphycins A and A2 (2) exhibited weak activities. The two major compounds isolated from the sample, laxaphycins A and B4, were shown to act synergistically to inhibit the growth of HCT116 colorectal cancer cells.

Odobromoamide, a terminal alkynyl bromide-containing cyclodepsipeptide from the marine cyanobacterium okeania sp.

The bioassay-guided fractionation of the Okinawan marine cyanobacterium Okeania sp. led to the isolation of the novel cyclodepsipeptide odobromoamide (1). The gross structure of 1 was determined by spectroscopic analyses, and its absolute stereochemistry was determined using a variety of different methods, including chemical derivatization and degradation followed by HPLC analysis. In addition, odobromoamide (1) exhibited broad-spectrum cytotoxicity against a human cancer cell line panel.

Urumamide, a novel chymotrypsin inhibitor with a β-amino acid from a marine cyanobacterium Okeania sp.

Urumamide, a novel cyclic depsipeptide that contains a β-amino acid, was isolated from a marine cyanobacterium Okeania sp. Its gross structure was determined by spectroscopic analyses, and the absolute configuration was established based on Marfey's analyses and chiral HPLC analyses of hydrolysis products. Biologically, urumamide inhibited the growth of human cancer cells. In addition, urumamide inhibited chymotrypsin.

Caldoramide, a Modified Pentapeptide from the Marine Cyanobacterium Caldora penicillata

The isolation, structure determination, and biological activities of a new linear pentapeptide, caldoramide (5), from the marine cyanobacterium Caldora penicillata from Florida are described. Caldoramide (5) has structural similarities to belamide A (4), dolastatin 10 (1), and dolastatin 15 (2). We profiled caldoramide against parental HCT116 colorectal cancer cells and isogenic cells lacking oncogenic KRAS or hypoxia-inducible factors 1α (HIF-1α) and 2α (HIF-2α). Caldoramide (5) showed differential cytotoxicity for cells containing both oncogenic KRAS and HIF over the corresponding knockout cells. LCMS dereplication indicated the presence of caldoramide (5) in a subset of C. penicillata samples.

Pembamide, a N-methylated linear peptide from a sponge Cribrochalina sp.

A new highly N-methylated linear peptide, pembamide (1), has been isolated from the marine sponge Cribrochalina sp. (family Niphatidae) collected off the coast of Pemba (Tanzania). The planar structure of 1 was assigned on the basis of extensive 1D and 2D NMR spectroscopy and mass spectrometry. The absolute configuration of the amino acid residues in 1 was determined by application of the Advanced Marfey's method. Compound 1 displayed significant cytotoxicity against three human tumor cell lines with GI50values in the micromolar range.

Systematic chemical mutagenesis identifies a potent novel apratoxin A/E hybrid with improved in vivo antitumor activity

Apratoxins are cytotoxic marine natural products that prevent cotranslational translocation early in the secretory pathway. We showed that apratoxins downregulate receptors and growth factor ligands, giving a one"two punch to cancer cells, particularly those that rely on autocrine loops. Through total synthesis, we tested the effects of amino acid substitutions, including alanine scanning, on the downregulation of receptor tyrosine kinases and vascular endothelial growth factor A (VEGF-A) and probed the stereospecificity of target engagement by epimerization of selected chiral centers. Differential effects on two types of secretory molecules suggest that the apratoxins' substrate selectivity with respect to inhibition of secretion may be tuned through structural modifications to provide tailored therapy. Our structure"activity relationship studies and medicinal chemistry efforts led to a potent inhibitor with in vivo efficacy in a colorectal tumor xenograft model without irreversible toxicity exerted by apratoxin A, demonstrating that this novel mechanism of action has therapeutic potential.

Evolved diversification of a modular natural product pathway: Apratoxins F and G, two cytotoxic cyclic depsipeptides from a palmyra collection of Lyngbya bouillonii

A collection of Lyngbya bouillonii from Palmyra Atoll in the Central Pacific, a site several thousand kilometers distant from all previous collections of this chemically prolific species of cyanobacterium, was found to contain two new cancer cell cytotoxins of the apratoxin family. The structures of the new compounds, apratoxins F and G, were determined by 1D and 2D NMR techniques in combination with mass spectrometric methods. Stereochemistry was explored by using chromatographic analyses of the hydrolytically released fragments in combination with NMR and optical rotation comparisons with known members of the apratoxin family. Apratoxins F and G add fresh insights into the SAR of this family because they incorporate an N-methyl alanine residue at a position where all prior apratoxins have possessed a proline unit, yet they retain high potency as cytotoxins to H-460 cancer cells with IC50 values of 2 and 14 nM, respectively. Additional assays using zone inhibition of cancer cells and clonogenic cells give a comparison of the activities of apratoxin F to apratoxin A. Additionally, the clonogenic studies in combination with maximum tolerated dose (MTD) studies provided insights as to dosing schedules that should be used for in vivo studies, and preliminary in vivo evaluation validated the predicted in vivo efficacy for apratoxin A. These new apratoxins are illustrative of a mechanism (the modification of an NRPS adenylation domain specificity pocket) for evolving a biosynthetic pathway so as to diversify the suite of expressed secondary metabolites.