Macrolide analogs and methods for identifying same

Organic compounds -- part of the class 532-570 series – Organic compounds – Unsubstituted hydrocarbyl chain between the ring and the -c-...

Reexamination Certificate

Rate now

  [ 0.00 ] – not rated yet Voters 0   Comments 0

Details

Reexamination Certificate

active

10710069

ABSTRACT:
Macrolide analogs and methods for identifying macrolide analogs capable of unregulated inhibition of actin filament dynamics are provided. A method according to the invention includes the steps of: (a) contacting F-actin with a candidate compound; and (b) assaying the candidate compound's ability to sever the F-actin and cap resulting F-actin (+)-ends. The candidate compound is identified as a macrolide analog where said candidate compound displays an ability to sever F-actin and, following severing, the resulting F-actin (+)-end is capped by the candidate compound thusly preventing subsequent G-actin incorporation. Severing and capping activities are unregulated; i.e., independent of at least physiologically-meaningful concentrations of phosphatidyl inositol and calcium.

REFERENCES:
patent: 5260224 (1993-11-01), Stossel
patent: 5508265 (1996-04-01), Stossel
patent: 5691160 (1997-11-01), Janmey
patent: 5985608 (1999-11-01), Luna
patent: 6312926 (2001-11-01), Shatkin
patent: 2002/0103112 (2002-08-01), Ferguson
Bubb, M.R., et al., “Swinholide A is a microfilament disrupting marine toxin that stabilizes actin dimers and severs actin filaments,” J Biol Chem. Feb. 24;270(8):3463-6 (1995).
D'Auria, M.V., Paloma, L.G. “Reidispongiolide A and B, Two new potent cytotoxic macrolides from the New Caladonian Sponge.” Tetrahedron 50(16): 4829-4834 (1994).
Guella, G., et al. “Sphinxolide, a 26-Membered Antitumoral Macrolide isolated from an unidentified Pacific Nudibranch.” Helvetica Chimica Acta, 72 :237-246 (1994).
Ishibashi, M., Moore, R.E., Patterson, G. “Scytophycins, Cytotoxic and antimoycotic agents from the cyanophyte Scytonema pseudohofmanni.” J. Org. Chem., 51:5300-5306 (1986).
Jefford, C.W. , Bernardinelli, G., “Structures and absolute configurations of the marine toxins Latrunculin A and Laulimalide.” Tetrahedron Letters, 37(2):159-162 (1996).
Kobayashi M, Tanaka J, Katori T, Kitagawa I. “Marine natural products. XXIII. Three new cytotoxic dimeric macrolides, swinholides B and C and isoswinholide A, congeners of swinholide A, from the Okinawan marine spongeTheonella swinhoei.” Chem Pharm Bull (Tokyo), Nov. 38(11):2960-6 (1996).
Marriott G, Zechel K, Jovin TM. “Spectroscopic and functional characterization of an environmentally sensitive fluorescent actin conjugate.” Biochemistry, 27(17):6214-20 (Aug. 23, 1996).
Marriott G, Miyata H, Kinosita K Jr. “Photomodulation of the nucleating activity of a photocleavable crosslinked actin dimer.” Biochem Int. 26(5):943-51 (Apr. 1992).
Matsunaga, S., et al. “Kabiramide C, a novel antifungal Macrolide from Nuidibranch Eggmasses.” J. Am. Chem. Soc. 108:847-849 (1986).
Morton W.M., et al.“Latrunculin alters the actin-monomer subunit interface to prevent polymerization.” Nat Cell Biol.2(6):376-8 (Jun. 2000).
Roesener, J.A., Scheuer, P.J. “Ulapualide A and B, Extraordinary antitumor macrolides from Nudibranch eggmasses.” J. Am. Chem. Soc. 108: 846-847 (1986).
Saito, S., Karaki, H. “A family of novel actin-inhibiting marine toxins.” Clinical and Experimental Pharmacology and Physiology, 23:743-746 (1996).
Tanaka, J., et al. “Marine Natural Products. XXIV The absolute stereostructure of misakinolide A a potent cytotoxic dineric macrolide from an Okinawan marine spongeTheonellasp.” Chem. Pharm. Bull. 38(11): 2967-2970 (1990).
Terry D.R, Spector I, Higa T, Bubb M.R. “Misakinolide A is a marine macrolide that caps but does not sever filamentous actin.” J Biol Chem.272(12):7841-5 (Mar. 21, 1997).
Wada S, et al.. “Actin-binding specificity of marine macrolide toxins, mycalolide B and kabiramide D.” J Biochem (Tokyo).123(5):946-52 (May 1998).
Yamada, K, et al. “Aplyronine A, a potent antitumor substance, and the congeners aplyronines B and C isolated from the sea hare aplysia kurodai.” J. Am. Chem. Soc. 115:11020-11021 (1993).
Zechel K. “The interaction of 6-propionyl-2-(NN-dimethyl)aminonaphthalene (PRODAN)-labelled actin with actin-binding proteins and drugs.” Biochem J., 290 (Pt 2):411-7 (Mar. 1, 1993).

LandOfFree

Say what you really think

Search LandOfFree.com for the USA inventors and patents. Rate them and share your experience with other people.

Rating

Macrolide analogs and methods for identifying same does not yet have a rating. At this time, there are no reviews or comments for this patent.

If you have personal experience with Macrolide analogs and methods for identifying same, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Macrolide analogs and methods for identifying same will most certainly appreciate the feedback.

Rate now

     

Profile ID: LFUS-PAI-O-3849411

  Search
All data on this website is collected from public sources. Our data reflects the most accurate information available at the time of publication.