10results about "Directed macromolecular evolution" patented technology

The present invention provides a method for constructing a cyclic compound library that overcomes the limitations of conventional ring-closing methods for cyclic compound libraries, has the advantages of milder ring-closing reaction conditions and high generality, can be used to construct monocyclic and bicyclic compound libraries, and involves few side reactions. [Solution] A cyclic compound library and its construction method are provided, which uses a solid support, a molecule containing a photocleavable group, a linker, a building block, a ring-closing A-terminal molecule, and a ring-closing B-terminal molecule at both ends of the reaction synthesis, and utilizes the decomposition of the solid support under light irradiation to complete ring closure of the amino acid residue structures of the ring-closing A-terminal molecule A and the ring-closing B-terminal molecule B through the action of cyclohydrolase. This method, which uses mild ring closure conditions, is more universal and expands the types of chemical reactions and the diversity of the encoded compound library.

To provide a conditionally active polypeptide having higher activity and / or selectivity in a specific environment and / or under a specific condition.SOLUTION: A non-naturally occurring polypeptide or an isolated polypeptide wherein the ratio of the activity of the assay at a first pH in presence of at least one species having a molecular weight of less than 900a. m.u. and a pKa that is a maximum of 4pH unit away from the first pH to the activity of the assay at a second pH in presence of the same at least one species is at least 1.3. The species has a pKa between the first pH and the second pH and may be a small molecule.SELECTED DRAWING: None

To provide a method for generating an antibody library.SOLUTION: (i) has at least two amino acid alterations in the light chain sequence when compared to the light chain amino acid sequence of the reference antibody, (ii) has at least two amino acid alterations in the heavy chain sequence when compared to the heavy chain amino acid sequence of the reference antibody, or (iii) has at least one amino acid alteration in the light chain sequence when compared to the light chain amino acid sequence of the reference antibody; And a variant of the reference antibody having at least one amino acid change in the heavy chain sequence when compared to the heavy chain amino acid sequence of the reference antibody, wherein each of the amino acid changes is in an amino acid residue independently encoded from a segment of the variant DNA sequence, and wherein the variant DNA segment differs from the corresponding segment of the reference antibody encoding DNA sequence by a point mutation in a DNA motif susceptible to deamination by a somatic hypermutation inducing enzyme.SELECTED DRAWING: None

A method for computational drug design using an evolutionary algorithm, comprises evaluating virtual molecules according to vector distance (VD) to at least one achievement objective that defines a desired ideal molecule. In one method the invention comprises defining a set of n achievement objectives (OA1-n), where n is at least one; defining a population (PG=0) of at least one molecule; selecting an initial population (Pparent) of at least one molecule (I1-In) from the population (PG=0); and evaluating members (I1-In) of the initial population (Pparent) against at least one of the n achievement objectives (OA1-x), where x is from 1 to n.

The present invention provides a method for constructing a cyclic compound library that overcomes the limitations of conventional ring-closing methods for cyclic compound libraries, has the advantages of milder ring-closing reaction conditions and high generality, can be used to construct monocyclic and bicyclic compound libraries, and involves few side reactions. [Solution] A cyclic compound library and its construction method are provided, which uses a solid support, a molecule containing a photocleavable group, a linker, a building block, a ring-closing A-terminal molecule, and a ring-closing B-terminal molecule at both ends of the reaction synthesis, and utilizes the decomposition of the solid support under light irradiation to complete ring closure of the amino acid residue structures of the ring-closing A-terminal molecule A and the ring-closing B-terminal molecule B through the action of cyclohydrolase. This method, which uses mild ring closure conditions, is more universal and expands the types of chemical reactions and the diversity of the encoded compound library.

In one aspect, the present disclosure provides a method for producing various virus-derived construct plasmids from starting plasmids (for example, the virus-derived construct plasmids of the present disclosure). In one embodiment, the method for producing virus-derived construct plasmids according to the present disclosure includes: a step for preparing a set of starting plasmids containing at least a portion of a nucleic acid sequence necessary for forming a virus-derived construct, the set of starting plasmids including a set of corresponding alternative unit nucleic acids, and the set of corresponding alternative unit nucleic acids including at least one set of corresponding alternative unit nucleic acids that contain a different nucleic acid sequence; a step for treating the set of starting plasmids with a restriction enzyme and preparing a mixed solution containing cleaved alternative unit nucleic acid fragments; a step for ligating the cleaved alternative unit nucleic acid fragments to form an integrated nucleic acid; and a step for causing the integrated nucleic acid to contact a transformed organism and thereby forming virus-derived construct plasmids.

The present disclosure relates to methods for generating antibody libraries, antibody libraries produced using such methods, and variant antibodies. Currently, methods for improving antibody binding (affinity maturation assays) involve screening large libraries of antibody variants (often >10 nucleotides) to identify a small subset of variants with improved properties. 10 The method involves obtaining the nucleotide sequence of the framework and complementarity-determining regions of a target antibody and identifying motifs recognized by a deaminating somatic hypermutation enzyme. A small library of variants incorporating one or more of these mutations is then generated. A relatively high percentage of the variants were found to have increased affinity. The technology of the present invention has been demonstrated with trastuzumab and cathepsin S antibodies, and the variants produced are also claimed.

Disclosed herein is an engineered fusion enzyme composed of a prokaryotic phage RNA polymerase (T7 RNAP) and a viral capping enzyme (NP868R) for the generation of RNA transcripts containing a 5' 7-methylguanylate cap.

Disclosed herein is an engineered fusion enzyme composed of a prokaryotic phage RNA polymerase (T7 RNAP) and a viral capping enzyme (NP868R) to generate RNA transcripts containing a 5' 7-methylguanylate cap.