Yasuhiko Muraoka

Total synthesis of deglyco-bleomycin A2

Abstract Deglyco-bleomycin A2, the aglycon of bleomycin A2, has been synthesized for the first time.

Induction of Apoptosis in Human Pancreatic Carcinoma Cells by a Synthetic Bleomycin-like Ligand

Histidine‐pyridine‐histidine‐3 (HPH‐3) is an oxygen‐activating ligand based on the structure of bleomycin. HPH‐3 induced the death of human pancreatic adenocarcinoma AsPC‐1 cells in 24 h, causing apoptotic morphology and internucleosomal degradation of DNA. HPH‐3‐induced cell death was not inhibited by antioxidants such as reduced glutathione and N‐acetylcysteine, whereas hydrogen peroxide‐induced cell death was inhibited by them, indicating that hydrogen peroxide is not involved in the induction of apoptosis by HPH‐3. Induction of apoptosis by HPH‐3 was inhibited by zinc and copper ions, indicating that chelation with ferrous ion is responsible for induction of apoptosis, as is the case in chelation by bleomycin to cleave DNA. Bleomycin A2 and its fragment having no DNA‐binding region, glycopeptide‐3, did not induce apoptosis in AsPC‐1 cells. Bleomycin A2 induced G2/M block in flow‐cytometric analysis, but HPH‐3 did not and instead induced an apoptotic pre‐G1 peak. Thus, HPH‐3 induced apoptosis in human pancreatic carcinoma cells, which is a unique characteristic among bleomycin‐related compounds.

Structure-affinity relationship study of bleomycins and shble protein by use of a chemical array

Natural product libraries for SAR studies: We used a chemical array platform to study the SARs of bleomycin (BLM) derivatives and Shble protein. The on‐chip SARs suggested that several domains are important for recognition of BLMs by Shble protein. In particular, the C‐terminal tail and the propionamide moiety in pyrimidoblamic acid (PBA) were shown to be important for the binding.

Sulphostin, a Novel Inhibitor of Dipeptidyl Peptidases IV (DPPIV) That Stimulates Hematopoiesis in Mice

CD26, a membrane-bound ectopeptidase, is known as an activated T cell marker with dipeptidyl peptidase IV (DPPIV) activity that has diverse functional roles in the regulation of peptide hormones, neuropeptides, chemokines and growth factors. We recently isolated a novel inhibitor of DPPIV, sulphostin, from culture broth of Streptomyces sp. MK251-43F3. We investigated herein the hematopoietic effect of sulphostin in mice and found that sulphostin induced the production of granulocyte colony-stimulating factor (G-CSF), stimulated myeloblasts in bone marrow, and increased neutrophil numbers in peripheral blood in both normal mice and mice with cyclophosphamide-induced leucopenia. Sulphostin desulfonate, in addition to sulphostin, has a similar inhibitory effect on DPPIV and stimulatory effect on neutrophils. These results suggest that DPPIV/CD26 might be a novel target for hematopoietic stimulation and DPPIV inhibitors including sulphostin and derivatives may be candidates for further development.

Corrigendum: Tripropeptins, novel antimicrobial agents produced by Lysobacter sp. II. structure elucidation

Correction to: The Journal of Antibiotics (2004) 57, 52–58; doi:10.7164/antibiotics.57.52 The authors of the above article did misjudgment the stereochemistry of tripropeptins-constituent serine residue which was determined by Marfey’s method using HPLC. From our recent analysis using advanced Marfey’s method (LC/MS) revealed that the stereochemistry of serine residue was proved to be D-form as shown below.

TA-3037A, A NEW INHIBITOR OF GLUTATHIONE S-TRANSFERASE, PRODUCED BY ACTINOMYCETES

TA-3037A, a new inhibitor of glutathione S-transferase was discovered in the fermentation broth of Streptomyces sp. TA-3037. It was purified by chromatography followed by solvent extraction and then isolated as yellow needles. TA-3037A has the molecular formula of C16H11NO4. It was competitive with the substrate, and the inhibition constant (Ki) was 4.9 microM.