摘要:
The invention concerns libraries of chemical compounds, that are useful in medicinal chemistry and related arts, their methods of manufacture and methods of their use. In one embodiment the individual chemical species of the library are synthesized aleatoricly, i.e, by a process involving chance. The chemical species of the library are used while attached to solid phase supports. The library differs from previously disclosed libraries that were intended to be screened while in solid phase in that each individual solid phase support or identifiable portion of a solid phase array displays many species of ligands, collectively termed a "set." The library is constructed so that each set contains a single invariant structure, common to all the species of ligands attached to the particular solid phase support, which is termed a "motif." The invention teaches that libraries of motifs can be employed advantageously compared to known libraries wherein a single species is present on each support.
摘要:
The invention relates to libraries of synthetic test compound attached to separate phase synthesis supports. In particular, the invention relates to libraries of synthetic test compound attached to separate phase synthesis supports that also contain coding molecules that encode the structure of the synthetic test compound. The molecules may be polymers or multiple nonpolymeric molecules. Each of the solid phase synthesis support beads contains a single type of synthetic test compound. The synthetic test compound can have backbone structures with linkages such as amide, urea, carbamate (i.e., urethane), ester, amino, sulfide, disulfide, or carbon--carbon, such as alkane and alkene, or any combination thereof. Examples of subunits suited for the different linkage chemistries are provided. The synthetic test compound can also be molecular scaffolds, such as derivatives of monocyclic of bicyclic carbohydrates, steroids, sugars, heterocyclic structures, polyaromatic structures, or other structures capable of acting as a scaffolding. Examples of suitable molecular scaffolds are provided. The invention also relates to methods of synthesizing such libraries and the use of such libraries to identify and characterize molecules of interest from among the library of synthetic test compound.
摘要:
The invention relates to libraries of synthetic test compound attached to separate phase synthesis supports that also contain coding molecules that encode the structure of the synthetic test compound. The molecules may be polymers or multiple nonpolymeric molecules. The synthetic test compound can have backbone structures with linkages such as amide, urea, carbamate (i.e., urethane), ester, amino, sulfide, disulfide, or carbon-carbon, such as alkane and alkene, or any combination thereof. Examples of subunits suited for the different linkage chemistries are provided. The synthetic test compound can also be molecular scaffolds, such as derivatives of monocyclic of bicyclic carbohydrates, steroids, sugars, heterocyclic structures, polyaromatic structures, or other structures capable of acting as a scaffolding. Examples of suitable molecular scaffolds are provided. The invention also relates to methods of synthesizing such libraries and the use of such libraries to identify and characterize molecules of interest from among the library of synthetic test compound.
摘要:
The present invention relates to methods for determining the amino acid composition, and more preferably the sequence, of a peptide using mass spectrometric techniques. The method is particularly useful for sequencing peptides isolated from natural sources or from libraries of peptides that have been prepared synthetically, and for peptides that are not amenable to Edman degradation sequencing. In one embodiment, the method for determining the amino acid composition or sequence of a peptide comprises determining the difference of the mass of the peptide from the mass of a deuterium-hydrogen exchanged peptide, and from this difference determining the number of exchangeable (labile) hydrogen atoms (protons). Candidate peptides having amino acid compositions or sequences that do not contain the observed number of exchangeable protons are eliminated. In another embodiment, synthesis of a portion of the peptides in a library of peptides is terminated after each coupling step, whereby a set of sequentially truncated fragments of each peptide is formed. Thus the sequence of the peptide can be determined by determining the difference in the molecular weight between each peptide or fragment thereof and the sequentially smaller fragment of the peptide.
摘要:
An apparatus for fragmenting nucleic acid. The apparatus includes a sample reservoir that comprises a fluid having nucleic acids. The apparatus can also include a shear wall that is positioned within the sample reservoir. The shear wall includes a porous core medium that has pores that are sized to permit nucleic acids to flow therethrough. The apparatus also includes first and second chambers that are separated by the shear wall. The first and second chambers are in fluid communication with each other through the porous core medium of the shear wall. Also, the apparatus may include first and second electrodes that are located within the first and second chambers, respectively. The first and second electrodes are configured to generate an electric field that induces a flow of the sample fluid. The nucleic acids move through the shear wall thereby fragmenting the nucleic acids.
摘要:
A simple, efficient apparatus and method for separating layers of immiscible or partially miscible liquids useful in methods of high-throughput combinatorial organic synthesis or parallel extraction of large libraries or megaarrays of organic compounds is disclosed. The apparatus and method are useful, whether as part of an automated, robotic or manual system for combinatorial organic synthesis or purification (extraction). In a preferred embodiment, an apparatus and method for separating layers of immiscible or partially miscible liquids compatible with microtiter plate type array(s) of reaction vessels is disclosed. Another application of centrifugation based liquid removal was found for washing the plates in biological assays or synthesis on modified substrates.
摘要:
An apparatus for high-throughput combinatorial synthesis of organic molecules including a reaction vessel for containing a combinatorial chemistry synthetic reaction, a liquid dispenser for dispensing the liquid, a liquid aspirator and an adjustment mechanism. The reaction vessel includes an ingress aperture allowing a liquid to enter into an interior of the vessel and an egress aperture for aspirating the liquid from the vessel. The liquid dispenser dispenses liquid through the ingress aperture. The liquid aspirator aspirates liquid through the egress aperture and includes a rotor for carrying the vessel and orbiting the vessel about an axis of rotation. The rotor is oriented generally in a horizontal plane and includes an adjustment mechanism for adjusting the angle of the vessel relative to the horizontal plane in response to the centrifugal force generated by orbiting the vessel about the axis or rotation. A method of combinatorial synthesis of organic molecules is also disclosed.
摘要:
An apparatus for high-throughput combinatorial syntheses of organic molecules including a reaction vessel for containing a combinatorial-chemistry synthetic reaction, a liquid dispenser for dispensing the liquid, a liquid aspirator and an adjustment mechanism. The reaction vessel includes an ingress aperture allowing a liquid to enter into an interior of the vessel and an egress aperture for aspirating the liquid from the vessel. The liquid dispenser dispenses liquid through the ingress aperture. The liquid aspirator aspirates liquid through the egress aperture and includes a rotor for carrying the vessel and orbiting the vessel about an axis of rotation. The rotor is oriented generally in a horizontal plane and includes an adjustment mechanism for adjusting the angle of the vessel relative to the horizontal plane in response to the centrifugal force generated by orbiting the vessel about the axis of rotation. A method of combinatorial synthesis of organic molecules is also disclosed.
摘要:
A simple, efficient apparatus and method for separation of solid and liquid phases useful in methods of high-throughput combinatorial organic synthesis of large libraries or megaarrays of organic compounds is disclosed. The apparatus and method are useful, whether as part of an automated, robotic or manual system for combinatorial organic synthesis. In a preferred embodiment, an apparatus and method of removal of liquid phase from solid phase compatible with microtiter plate type array(s) of reaction vessels is disclosed.
摘要:
Methods of generating nucleic acid fragments of substantially uniform length from sample nucleic acids comprising linearly stretching the sample nucleic acids over a substrate having a plurality of cleavage regions separated by relatively consistent distances, cleaving the linearly stretched sample nucleic acids at the cleavage regions, and collecting the resulting nucleic acid fragments. The method may further include collecting and concentrating the resultant nucleic acid fragments of substantially uniform length.