A method for determining if a peptide binds or is capable of binding to a ubiquitin protein ligase (E3) and thereby leads to degradation of a test protein, wherein the peptide is between about 7 and 110 amino acids in length, the method comprising: - providing in a eukaryotic cell a candidate peptide functionally linked to a test protein, under conditions enabling ubiquitination of proteins by an E3; and - detecting the amount of test protein present in the cell; whereby, a reduced amount of the test protein determines the candidate peptide as a peptide that binds or is capable of binding to an E3 (an E3-binding peptide); wherein the candidate peptide is functionally linked to the test protein and the candidate peptide is comprised in at least one hybrid polypeptide as a domain; wherein the hybrid polypeptide comprises a domain being a test protein or a test protein binding (poly)peptide; and a domain being a peptide linker; and wherein the amino acid sequence of the test protein is genetically engineered to comprise a plurality of lysine residues, wherein the test protein is genetically engineered to comprise an N-terminal lysine-rich region derived from human nitric oxide synthase (NOS1); and wherein the candidate peptide functionally linked to the test protein is provided as a member of a library of candidate peptides, suitably each functionally linked to the test protein; and wherein the candidate peptides comprised in the library have a length of between about 7 and 110 amino acids, and have an amino acid sequence being a region of a sequence selected from the amino acid sequence of a naturally occurring protein of one or more organisms; wherein the library comprises a plurality of at least 5,000 different such peptides, and wherein the amino acid sequence of each of at least 50 of such peptides is a sequence region of the amino acid sequence of a different protein of a plurality of different such naturally occurring proteins. - providing in a eukaryotic cell a candidate peptide functionally linked to a test protein, under conditions enabling ubiquitination of proteins by an E3; and - detecting the amount of test protein present in the cell; whereby, a reduced amount of the test protein determines the candidate peptide as a peptide that binds or is capable of binding to an E3 (an E3-binding peptide); wherein the candidate peptide is functionally linked to the test protein and the candidate peptide is comprised in at least one hybrid polypeptide as a domain; wherein the hybrid polypeptide comprises a domain being a test protein or a test protein binding (poly)peptide; and a domain being a peptide linker; and wherein the amino acid sequence of the test protein is genetically engineered to comprise a plurality of lysine residues, wherein the test protein is genetically engineered to comprise an N-terminal lysine-rich region derived from human nitric oxide synthase (NOS1); and wherein the candidate peptide functionally linked to the test protein is provided as a member of a library of candidate peptides, suitably each functionally linked to the test protein; and wherein the candidate peptides comprised in the library have a length of between about 7 and 110 amino acids, and have an amino acid sequence being a region of a sequence selected from the amino acid sequence of a naturally occurring protein of one or more organisms; wherein the library comprises a plurality of at least 5,000 different such peptides, and wherein the amino acid sequence of each of at least 50 of such peptides is a sequence region of the amino acid sequence of a different protein of a plurality of different such naturally occurring proteins. <EOS>