25-11-2021 дата публикации
Номер: US20210363214A1
Принадлежит:
De novo designed multi-pass transmembrane polypeptides are described, that include 2 or more transmembrane domains that are each between 15 and 35 amino acids in length, include one or more polar residues, and include at least 60%, 65%, 70%, 75%, 80%, 85%, 90%, or more hydrophobic amino acid residues. 1. A non-naturally occurring polypeptide comprising the general formula X1-TM1-X2-TM2-X3 , whereinX1 is an optional first peptide domainTM1 is a first transmembrane peptide of between 15 and 35 amino acids in length and capable of spanning a biological membrane, wherein (a) the first residue of TM1 is R or K; (b) the last residue of TM1 is W, Y, or L; and (c) at least 60%, 65%, 70%, 75%, 80%, 85%, 90%, or more of the internal residues are hydrophobic;X2 comprises a first connecting peptide;TM2 is a second transmembrane peptide of between 15 and 35 amino acids in length and capable of spanning a biological membrane, wherein (a) the first residue of TM2 is W, T, Q, or Y; (b) the last residue of TM2 is R or K; and (c) at least 60%, 65%, 70%, 75%, 80%, 85%, 90%, or more of the internal residues are hydrophobic; andX3 is an optional second peptide domain;wherein TM1 includes at least a first interior polar amino acid residue that is capable of forming a hydrogen bond with a first interior polar amino acid residue present in TM2.2. The polypeptide of claim 1 , wherein TM1 and TM2 each include at least two interior polar amino acid residues capable of hydrogen bonding with interior amino acids of the other TM domain.35.-. (canceled)6. The polypeptide of claim 1 , wherein TM1 comprises the internal amino acid sequence XXXXX (SEQ ID NO: 1) claim 1 , wherein “X” is any hydrophobic amino acid claim 1 , or wherein TM1 comprises the internal amino acid sequence IFAIVL (SEO ID NO: 2).7. (canceled)9. (canceled)10. The polypeptide of claim 1 , wherein TM2 comprises the amino acid sequence XL(L/V)XXI(L/M)XLVXXI(V/I)X (SEQ ID NO: 15) claim 1 , wherein X is any hydrophobic amino acid ...
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