摘要:
Alphabodies that specifically bind to cytokines or growth factor and/or their receptors, as well as polypeptides that comprise or essentially consist of such Alphabodies. Further nucleic acids encoding such Alphabodies; methods for preparing such Alphabodies and polypeptides; host cells expressing or capable of expressing such Alphabodies and polypeptides; compositions, and in particular pharmaceutical compositions, that comprise such Alphabodies, polypeptides, nucleic acids and/or host cells; and uses of such Alphabodies or polypeptides, nucleic acids, host cells and/or compositions, in particular for prophylactic, therapeutic or diagnostic purposes.
摘要:
The invention provides single-chain Alphabody library comprising at least 100 different-sequence single-chain Alphabody polypeptides, wherein said Alphabody polypeptides differ from each other in at least one of a defined set of 5 to 20 variegated amino acid residue positions, and wherein at least 70% but not all of said variegated amino acid residue positions are located either in the loop, helix surface or linker region of the Alphabody. The invention further provides methods for use of the Alphabody libraries and Alphabodies obtainable by the methods of the invention.
摘要:
The invention provides single-chain Alphabody library comprising at least 100 different-sequence single-chain Alphabody polypeptides, wherein said Alphabody polypeptides differ from each other in at least one of a defined set of 5 to 20 variegated amino acid residue positions, and wherein at least 70% but not all of said variegated amino acid residue positions are located either in the loop, helix surface or linker region of the Alphabody. The invention further provides methods for use of the Alphabody libraries and Alphabodies obtainable by the methods of the invention.
摘要:
The present invention is related to a non-natural, thermodynamically stable, proteinaceous scaffold consisting of three non-covalently associated peptides, wherein each peptide sequence comprises less than fifty amino acid residues and wherein at least 50% of the said residues are substitutable amino acids into at least ten different amino acid residue types. The present invention is further related to a non-natural, triple-stranded, parallel alpha-helical coiled coil scaffold wherein each of the three constituting peptide sequences comprise between 2 and 7 consecutive heptad repeats of the formula cxxcxxx (SEQ ID NO: 10), wherein at least 70% of the core c-residues are isoleucines, wherein all non-core x-residues are alanines, and wherein the constituting peptide sequences remain associated under physical conditions that are significantly different from physiological conditions.
摘要翻译:本发明涉及由三种非共价相关肽组成的非天然的热力学稳定的蛋白质支架,其中每个肽序列包含少于50个氨基酸的残基,并且其中至少50%的所述残基是可取代的氨基酸 至少十种不同的氨基酸残基类型。 本发明进一步涉及非天然的三链平行α-螺旋卷曲线圈支架,其中三个构成肽序列中的每一个包含2至7个连续的式cxxcxxx(SEQ ID NO:10)的七重复重复序列, 其中至少70%的核心c残基是异亮氨酸,其中所有非核心x残基都是丙氨酸,并且其中构成的肽序列在与生理条件显着不同的物理条件下保持相关。
摘要:
The present invention relates to a method for structure-based prediction of properties of peptides and peptide analogs in complex with major histocompatibility (MHC) class I and class II molecules. The said properties mainly relate to the three-dimensional structure of an MHC/peptide complex and the binding affinity of a peptide for an MHC receptor. The invention further relates to a computer program and a device therefor. The invention further relates to data produced by a method of the invention. The invention further relates to peptides and peptide analogs predicted to bind to target-MHC molecules. The present invention thus relates to the field of immunology, with possible applications in manufacture of vaccinates, de-immunization of proteins, and manufacture of therapeutic agents, especially immuno-therapeutic agents.
摘要:
The invention provides methods for the production of single-chain Alphabody polypeptides having detectable binding affinity for, or detectable in vitro activity on, a viral protein of interest, which comprising the step of producing a single-chain Alphabody library comprising at least 100 different-sequence single-chain Alphabody polypeptides, wherein said Alphabody polypeptides differ from each other in at least one of a defined set of 5 to 20 variegated amino acid residue positions, and wherein said variegated amino acid residue positions are located at specific positions in one or more of the alpha-helices of the Alphabody or the linker fragment connecting two consecutive alpha-helices of the Alphabody polypeptides. The invention further provides Alphabodies obtainable by the methods of the invention and uses thereof.
摘要:
Single-chain Alphabodies that comprise an alpha-helical binding region which mediates binding to a first fusion-driving region of a class-1 viral fusion protein and which structurally mimics a second fusion-driving region of said class-1 viral fusion protein, wherein said first and second fusion-driving regions of said class-1 viral fusion protein are regions which interact to drive the fusion between a virus displaying said class-1 viral fusion protein and a target cell.
摘要:
The present invention is related to a quantitative structure-based affinity scoring method for peptide/protein complexes. More specifically, the present invention comprises a method that operates on the basis of a highly specific force field function (e.g. CHARMM) that is applied to all-atom structural representations of peptide/receptor complexes. Peptide side-chain contributions to total affinity are scored after detailed rotameric sampling followed by controlled energy refinement. The method of the invention further comprises a de novo approach to estimate dehydration energies from the simulation of individual amino acids in a solvent box filled with explicit water molecules and applying the same force field function as used to evaluate peptide/receptor complex interactions.
摘要:
A method for generating information related to the molecular structure of a biomolecule, comprising the steps of: (a) receiving a three-dimensional representation of said molecular structure, comprising a first set of residue portions and a template; and (b) modifying the representation of step (a) by at least one optimization cycle. Each optimization cycle comprises the steps of: (b1) perturbing a first representation of the molecular structure by modifying the structure of one or more of the first set of residue portions; (b2) relaxing the perturbed representation by optimizing the structure of one or more of the non-perturbed residue portions of the first set with respect to the one or more perturbed residue portions; (b3) evaluating the perturbed and relaxed representation of the molecular structure by using an energetic cost function and replacing the first representation by the perturbed and relaxed representation if the latter's global energy is more optimal than that of the first representation; and the method further comprises the steps of (c) terminating the optimization process according to step (b) when a predetermined termination criterion is reached; and (d) outputting to a storage medium or to a consecutive method a data structure comprising information extracted from step (b).