| Cleavable surfactants and methods of use thereof -> Monitor Keywords |
|
|
  Cleavable surfactants and methods of use thereofUSPTO Application #: 20060240562Title: Cleavable surfactants and methods of use thereof Abstract: Cleavable compositions and methods of use especially in MALDI MS analysis of hydrophobic proteins. (end of abstract)
Agent: Stites & Harbison PLLC - Nashville, TN, US Inventors: Richard M. Caprioli, Ned A. Porter, Jeremy L. Norris USPTO Applicaton #: 20060240562 - Class: 436086000 (USPTO) Related Patent Categories: Chemistry: Analytical And Immunological Testing, Peptide, Protein Or Amino Acid The Patent Description & Claims data below is from USPTO Patent Application 20060240562. Brief Patent Description - Full Patent Description - Patent Application Claims
FIELD OF THE INVENTION [0001] The present invention relates generally to cleavable detergents or surfactants and methods of use thereof including sample isolation, solubilization, emulsification, and analysis. Furthermore, the present invention relates to cleavable surfactants which are useful for sample preparation, but which can be cleaved for removal or to yield cleavage products which have additional useful properties, including for matrix assisted laser desorption ionization mass spectroscopy (MALDI MS) analysis of hydrophobic molecules including natural and synthetic polymers and polypeptides. [0002] The cleavable detergents or surfactants of the present invention, among other things in additional embodiments, improve the quality of MALDI MS analyses of proteins, including high molecular weight proteins associated with biological tissue. BACKGROUND OF THE INVENTION [0003] Proteomics, the study of proteins and their functions, is currently a focus of both university and commercial investment as each discovery in proteomics holds the potential to unlock yet another advance in medical science. The extreme variability in the chemistry of proteins in biological systems and especially in mammals, presents special problems. [0004] A recurring problem with respect to proteomics involves the poor solubility of a large percentage of proteins such as those found in lipid membranes and other hydrophobic areas of the cell or in the cellular environment. This is because many of the systems developed for the study of proteins are geared to analysis in an aqueous environment. To isolate hydrophobic proteins or hydrophobic protein domains, surfactants (detergents, such as sodium dodecyl sulfate (SDS) or triton X) are commonly employed. Surfactants generally have a polar head group and a hydrophobic tail group and encapsulate hydrophobic proteins wherein the hydrophobic tail is in contact with the hydrophobic protein and the polar groups are in contact with the water. Thus, hydrophobic proteins and polypeptides are sequestered in a coating of detergent wherein the complex is soluble in an aqueous environment. [0005] However, many analytical systems are sensitive to the presence of surfactants. For example, SDS and triton X suppress the analyte signal during matrix assisted laser desorption ionization mass spectrometry (MALDI MS) analysis. Signal suppression from surfactant contamination is contemplated to result from physical and chemical blockage of the ionization/desorption process of MALDI MS. [0006] What is needed are surfactant compositions and methods suitable for MALDI-MS analyses, and other analyses, of hydrophobic molecules including natural and synthetic polymers and polypeptides/proteins. [0007] International Publication WO 00/70334 to Lee et al., discloses certain surfactants and results for electrospray mass spectroscopy (MS) analysis of myoglobin in the presence of certain of the surfactants. [0008] U.S. Pat. No. 4,713,486 to Buckle discloses certain arachidonic acid analogues, including certain cinnamates, stated to be useful in the treatment of allergic diseases. [0009] U.S. Pat. No. 5,114,851 to Porter et al., discloses certain light activated acyl-enzymes. [0010] U.S. Pat. No. 5,218,137 to Porter et al., discloses certain compounds useful as an intermediate for making light-activatable acyl-enzymes. [0011] Also see U.S. Pat. No. 5,808,300 to Caprioli, incorporated herein by reference, for a discussion of MALDI MS. [0012] Additional background information may be found in the following publications: Kyte et al., J. Mol. Biol. (1982) 157(1):105-32; March's Advanced Organic Chemistry: Reactions, Mechanisms, and Structure, 5.sup.th Ed. by Michael B. Smith and Jerry March, John Wiley & Sons, Publishers; Wuts et al. (1999) Protective Groups in Organic Synthesis, 3.sup.rd Ed. , John Wiley & Sons, Publishers; Behforouz, M.; Kerwood, J. E. Alkyl and Aryl Sulfenimides. J. Org. Chem., 34 (1), 51-55 (1969); and Harpp, D. N.; Ash, D. K.; Back, T. G.; Gleason, J. G.; Orwig, B. A.; VanHorn, W. F. A New Synthesis of Unsymmetrical Disulifdes. Tetrahedron Letters, 41, 3551-3554 (1970). SUMMARY OF THE INVENTION [0013] This invention relates to the treatment of a sample, such as a tissue section from a plant or animal, with a compound or mixture of compounds that would perform multi-functional roles in the preparation of these samples for analysis, e.g., mass spectrometry or chromatography, at designed times determined by treatment conditions. These compounds would be able to function as a surfactant or detergents in helping solubilize hydrophobic or other non-soluble compounds. Due to built in cleavable bonds, appropriate treatment of the sample, for example, with acid, base, heat, light, etc., would then cause decomposition of the agent to two or more smaller parts, each of which does not materially interfere with the analysis. Further, each part may in itself perform a further function; for example, one part may help solubilize compounds present in the mixture and the other, for MALDI mass spectrometry, may form crystals in the same way matrix acts in common MALDI analysis. [0014] Accordingly, the present invention provides, in part, compositions and methods including, but not limited to: novel cleavable surfactants and methods for preparing cleavable surfactants and using them in proteomic analysis including for matrix assisted laser desorption ionization mass spectrometry (MALDI MS). Certain compositions disclosed herein include the surprising properties of being a surfactant that yields one or more analyte assisting molecules upon cleavage including a MALDI matrix composition and a volatile solvent. No aspect or embodiment of the present invention including any claim is bound by theory or mechanism. [0015] In embodiments of the present invention, compounds of the present invention may be constructed or synthesized in two parts, connected by a linking group that can be cleaved by the addition of another chemical agent or energy source. The portion of the compound that would act as a matrix after cleavage would be polar in nature and, in certain embodiments, be a cinnamic acid analog or similar compound. The second part of the molecule may be for example, a hydrophobic molecule such as hexane or octane alkyl group with a functional group such as thiol or alcohol. After cleavage, this compound may act as a solvent, allowing solubilization of other compounds present including the other part of the agent. The linkage between the parts may comprise a bold such as, for example, a disulfide, thio ester, etc. that would preferably be stable until exposed to a chemical or energy source whereby it would cleave into the two parts described above. [0016] Advantages described in certain aspects and embodiments of the present invention include that hydrophobic elements, such as certain polymers, polypeptides, proteins, and components of cell samples, and tissue samples, etc. can be isolated and extracted using a detergent or surfactant and then the surfactant compound is treatable or treated to yield cleavage compositions with different and useful properties. For example, certain novel surfactant compositions described herein lose their surfactant properties upon cleavage of a linker group and the cleavage products are easily removed from the sample especially in comparison to the parent compounds or other surfactants which tend to stick to hydrophobic molecules. [0017] One aspect of the present invention comprises surfactants including a MALDI MS matrix joined to a hydrophobic tail group by a cleavable linker. [0018] Another aspect of the present invention provides cleavable surfactants having a cinnamic group joined to a hydrophobic tail group by a cleavable linker. Still another aspect of the invention provides a sinapinic group and a hydrophobic group joined by a cleavable linker. In certain embodiments, the linker comprises a disulfide group, a thioester group, or a ketal group. In certain preferred embodiments, the linker is a thioester group. [0019] Another aspect of the present invention provides novel cleavable surfactants having a polar head group joined to a hydrophobic tail by at least one cleavable linker. [0020] Another aspect of the invention provides certain novel cleavable surfactants which lose their surfactant properties upon a cleavage. [0021] Still another aspect of the present invention provides methods for using surfactants (novel to this invention or otherwise) for analysis of molecules, proteins, polypeptides, polymers and the like that are hydrophobic or include hydrophobic regions or domains. Continue reading... Full patent description for Cleavable surfactants and methods of use thereof Brief Patent Description - Full Patent Description - Patent Application Claims Click on the above for other options relating to this Cleavable surfactants and methods of use thereof patent application. ###  How KEYWORD MONITOR works... a FREE service from FreshPatents1. Sign up (takes 30 seconds). 2. Fill in the keywords to be monitored. 3. Each week you receive an email with patent applications related to your keywords. Start now! - Receive info on patent apps like Cleavable surfactants and methods of use thereof or other areas of interest. ### Previous Patent Application: Biomarkers for diagnosing alzheimer's disease Next Patent Application: Electronic system for tracking and monitoring articles to be sterilized and associated method Industry Class: Chemistry: analytical and immunological testing ### FreshPatents.com Support Thank you for viewing the Cleavable surfactants and methods of use thereof patent info. IP-related news and info Results in 3.91537 seconds Other interesting Feshpatents.com categories: Accenture , Agouron Pharmaceuticals , Amgen , AT&T , Bausch & Lomb , Callaway Golf |
||
