Showing papers by "Serge Muyldermans published in 2001"
TL;DR: Because of their smaller size and the above properties, the VHH clearly offer added-value over conventional antibody fragments, they are expected to open perspectives as enzyme inhibitors and intrabodies, as modular building units for multivalent or multifunctional constructs, or as immuno-adsorbents and detection units in biosensors.
763 citations
TL;DR: The easy generation steps and the biophysical properties of these bispecific and bivalent constructs based on camel single-domain antibody fragments makes them particularly attractive for use in therapeutic or diagnostic programs.
390 citations
TL;DR: The mutations and structural adaptations that have taken place to reshape a VH of a Vh-VL pair into a single-domain VHH with retention of a sufficient variability are reviewed.
388 citations
TL;DR: Addition of the VHHs to the TEM-1 β-lactamase, expressed on the surface of bacteria, leads to a higher ampicillin sensitivity of the bacteria, which could generate multiple potent inhibitors for all types of β- lactamases.
Abstract: Small, soluble single-domain fragments derived from the unique variable region of dromedary heavy-chain antibodies (VHHs) against enzymes are known to be potent inhibitors. The immunization of dromedaries with the TEM-1 and BcII β-lactamases has lead to the isolation of such single-domain antibody fragments specifically recognizing and inhibiting those β-lactamases. Two VHHs were isolated that inhibit TEM-1 and one BcII inhibiting VHH was identified. All inhibitory VHHs were tight-binding inhibitors. The 50% inhibitory concentrations were determined for all inhibitors and they were all in the same range as the enzyme concentration used in the assay. Addition of the VHHs to the TEM-1 β-lactamase, expressed on the surface of bacteria, leads to a higher ampicillin sensitivity of the bacteria. This innovative strategy could generate multiple potent inhibitors for all types of β-lactamases.
360 citations
TL;DR: The crystal structures of an antibody fragment derived from a camel heavy chain antibody against carbonic anhydrase, free and in complex with antigen are reported, Surprisingly, this single-domain antibody interacts with nanomolar affinity with the antigen through its third hypervariable loop (19 amino acids long).
233 citations
TL;DR: This chapter focuses on the steps that are involved in the ontogeny of a heavy-chain antibody (HCAb), starting from distinct genes, and the primary and tertiary structure of the antigen-specific VHHs is used to explain their biochemical properties.
Abstract: Publisher Summary This chapter focuses on the steps that are involved in the ontogeny of a heavy-chain antibody (HCAb), starting from distinct genes. HCAb is defined as an immunoglobulin devoid of light (L) chains. The presence of HCAbs in human serum is reported as a pathological disorder. It seems that, besides the absence of L chain, the heavy (H) chain of the HCAb is truncated. The current methods that are employed to isolate antigen-specific VHHs, either polyclonal or monoclonal, are reviewed in the chapter. The primary and tertiary structure of the antigen-specific VHHs is used to explain their biochemical properties. Their soluble behavior, stability, diverse structural repertoire of the antigen-binding site, and antigen-binding capacity are emphasized. The observation of VHHs recognizing epitopes that are less immunogenic for conventional Fv fragments (for example—active site of enzymes) might also lead to a number of applications. In addition, biotechnological fields where VHHs might have competitive advantages over scFvs or any other antigen-binding fragment derived from conventional antibodies are also summarized in the chapter.
157 citations
TL;DR: The results show that protein-protein interface characteristics can vary significantly between different specimens of the same high-affinity antibody-protein antigen complex, and consideration should be given to this type of observation when trying to establish general protein- protein interface characteristics.
60 citations