Bryostatin

The structures of the bryostatins were determined by a combination of singlecrystal X-ray diffraction analysis and/or a series of detailed spectroscopic analyses. 

Department of Chemistry and Biochemistry, University of Texas, Austin, Austin, TX 78712, USA e-mail mkrische mail.utexas.edu 

As described in several monographs [4], bryostatin 1 exhibits significant in vitro and in vivo antineoplastic activity against a range of tumor cell lines including murine leukemia, B-cell lymphoma, reticulum cell sarcoma, ovarian carcinoma, and melanoma. It is also effective in the modulation of apoptotic function [5], the reversal of multidrug resistance [6], and stimulation of the immune system [7]. These unique features displayed by bryostatin 1 are attributed to its high affinity for protein kinase C (PKC) isozymes and its ability to selectively modulate their functions [8]. PKCs are a type of intracellular serine and threonine kinase that 

C26 pharmacophoric element C3, C11 transannular hydrogen bonding C7, C20 tunable substituents C8 gem-dimethyl crucial for bryostatin-like biological respose 

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Bryamycin Bryostatin 1 BSA-SILICA B-stage B-stage resins B. subtilis 66333 BTEPE [37853-59-1]... 

Bryostatins are another class of compounds that bind to the Cl domain and result in acute activation of PKC. However, unlike phorbol esters, these marine natural products have antitumor effects. Bryostatins are currently in phase II clinical trials and show promise as anticancer drugs, particularly when combined with other adjuvant therapy. 

Figure 3.3. Bryostatin 2. Bryostatin 2 (C HggOjg) is a biologically active marine natural product which may have useful anti-cancer properties. It was recently synthesised at Harvard by Professor David Evans and his research group. In this illustration, all of the hydrogen atoms are omitted in order to simplify the structure. The lower diagram shows a low energy conformation of bryostatin 2, but it may only be a local minimum and not a global minimum. Many other conformations are accessible at room temperature.

Figure 3.4. Pentane. The diagram shows the four minimum-energy conformations of pentane. The global minimum is on the far left. Reflection and rotation of some of these geometries worrld generate more structures, but nothing with a different energy. Pentane is a simple molecule. More complicated molecules have many more conformations. Bryostatin 2 and PM-toxin A have so many mirrimtrm-energy conformations that to list them all would be a major undertaking and would require a large library to store the result.

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