| Title: |
Chemical synthesis and spontaneous folding of a multidomain protein:Anticoagulant microprotein S |
| Authors: |
Hackeng, TM; Fernandez, JA; Dawson, PE; Kent, SBH; Griffin, JH |
| Source: |
Hackeng, TM, Fernandez, JA, Dawson, PE, Kent, SBH & Griffin, JH 2000, 'Chemical synthesis and spontaneous folding of a multidomain protein : Anticoagulant microprotein S', Proceedings of the National Academy of Sciences of the United States of America, vol. 97, no. 26, pp. 14074-14078. https://doi.org/10.1073/pnas.260239797 |
| Publication Year: |
2000 |
| Collection: |
Maastricht University Research Publications |
| Subject Terms: |
PHASE PEPTIDE-SYNTHESIS; C4B-BINDING PROTEIN; THROMBOTIC DISEASE; PURPURA FULMINANS; C DEFICIENCY; FACTOR-IX; BINDING; PLASMA; DOMAIN; PURIFICATION |
| Description: |
Because of recent high-yield native ligation techniques, chemical synthesis of larger multidomain bioactive proteins is rapidly coming within reach. Here we describe the total chemical synthesis of a designed "microprotein S," comprising the gamma -carboxyglutamic acid-rich module, the thrombin-sensitive module, and the first epidermal growth factor-like module of human plasma protein S (residues 1-116). Synthetic microprotein S expressed anticoagulant cofactor activity for activated protein C in the down-regulation of blood coagulation, and the anticoagulant activity of microprotein S was not neutralized by C4b-binding protein, a natural inhibitor of native protein S in plasma. The correct folding of this complex multidomain protein was enhanced compared with individual modules because the gamma -carboxyglutamic acid-rich module and the thrombin-sensitive module markedly facilitated correct folding of the first epidermal growth factor-like module compared with folding of the first epidermal growth factor-like module alone. These results demonstrate that total chemical synthesis of proteins offers an effective way to generate multidomain biologically active proteins. |
| Document Type: |
article in journal/newspaper |
| Language: |
English |
| ISSN: |
0027-8424; 1091-6490 |
| Relation: |
info:eu-repo/semantics/altIdentifier/wos/000165993700018; info:eu-repo/semantics/altIdentifier/pissn/0027-8424; info:eu-repo/semantics/altIdentifier/eissn/1091-6490 |
| DOI: |
10.1073/pnas.260239797 |
| Availability: |
https://cris.maastrichtuniversity.nl/en/publications/ed521250-7148-4921-bdfe-78fe244f0f17; https://doi.org/10.1073/pnas.260239797; https://europepmc.org/articles/pmc18873?pdf=render |
| Rights: |
info:eu-repo/semantics/openAccess |
| Accession Number: |
edsbas.58995E29 |
| Database: |
BASE |