Drug discovery: a jump-start for electroceuticals
Already, devices that harness electrical impulses are used to treat disease. Pacemakers and
defibrillators save millions of lives each year; deep-brain stimulation dramatically improves
the quality of life for people with Parkinson's disease and depress ion; sacral-nerve …
defibrillators save millions of lives each year; deep-brain stimulation dramatically improves
the quality of life for people with Parkinson's disease and depress ion; sacral-nerve …
Aggregation-resistant domain antibodies selected on phage by heat denaturation
L Jespers, O Schon, K Famm, G Winter - Nature biotechnology, 2004 - nature.com
We describe a method for selecting aggregation-resistant proteins by heat denaturation.
This is illustrated with antibody heavy chain variable domains (dAbs), which are prone to
aggregate 1, 2. The dAbs were displayed multivalently at the infective tip of filamentous …
This is illustrated with antibody heavy chain variable domains (dAbs), which are prone to
aggregate 1, 2. The dAbs were displayed multivalently at the infective tip of filamentous …
Catalytic in vivo protein knockdown by small-molecule PROTACs
…, LN Casillas, BJ Votta, W Den Besten, K Famm… - Nature chemical …, 2015 - nature.com
The current predominant therapeutic paradigm is based on maximizing drug-receptor
occupancy to achieve clinical benefit. This strategy, however, generally requires excessive
drug concentrations to ensure sufficient occupancy, often leading to adverse side effects …
occupancy to achieve clinical benefit. This strategy, however, generally requires excessive
drug concentrations to ensure sufficient occupancy, often leading to adverse side effects …
Bioelectronic medicines: a research roadmap
With the rapid rise in technology for the precision detection and modulation of electrical
signalling patterns in the nervous system, a new class of treatments known as bioelectronic
medicines seems within reach1. Specifically, the peripheral nervous system will be at the …
signalling patterns in the nervous system, a new class of treatments known as bioelectronic
medicines seems within reach1. Specifically, the peripheral nervous system will be at the …
Thermodynamically stable aggregation-resistant antibody domains through directed evolution
Protein aggregates are usually formed by interactions between unfolded or partially
unfolded species, and often occur when a protein is denatured by, for example, heat or low
pH. In earlier work, we used a Darwinian selection strategy to create human antibody …
unfolded species, and often occur when a protein is denatured by, for example, heat or low
pH. In earlier work, we used a Darwinian selection strategy to create human antibody …
Repertoires of aggregation-resistant human antibody domains
We recently described a method for the generation of a large human domain antibody
repertoire involving combinatorial assembly of CDR building blocks from a smaller
repertoire comprising a high frequency of aggregation-resistant antibody domains. Here we …
repertoire involving combinatorial assembly of CDR building blocks from a smaller
repertoire comprising a high frequency of aggregation-resistant antibody domains. Here we …
Sequence determinants of protein aggregation in human VH domains
K Dudgeon, K Famm, D Christ - Protein Engineering, Design & …, 2008 - academic.oup.com
Human antibody variable heavy (VH) domains tend to aggregate upon denaturation, for
instance, by heat or acid. We have previously demonstrated that domains resisting protein
aggregation can be selected from CDR-only repertoires by phage display. Here we …
instance, by heat or acid. We have previously demonstrated that domains resisting protein
aggregation can be selected from CDR-only repertoires by phage display. Here we …
Tapping diversity lost in transformations—in vitro amplification of ligation reactions
Molecular evolution is a powerful means of engineering proteins. It usually requires the
generation of a large recombinant DNA library of variants for cloning into a phage or plasmid
vector, and the transformation of a host organism for expression and screening of the variant …
generation of a large recombinant DNA library of variants for cloning into a phage or plasmid
vector, and the transformation of a host organism for expression and screening of the variant …
Conserved and Nonconserved Residues in the Substrate Binding Site of 7,8-Diaminopelargonic Acid Synthase from Escherichia coli Are Essential for Catalysis
J Sandmark, AC Eliot, K Famm, G Schneider… - Biochemistry, 2004 - ACS Publications
The vitamin B6-dependent enzyme 7, 8-diaminopelargonic acid (DAPA) synthase catalyzes
the antepenultimate step in the synthesis of biotin, the transfer of the α-amino group of S-
adenosyl-l-methionine (SAM) to 7-keto-8-aminopelargonic acid (KAPA) to form DAPA. The …
the antepenultimate step in the synthesis of biotin, the transfer of the α-amino group of S-
adenosyl-l-methionine (SAM) to 7-keto-8-aminopelargonic acid (KAPA) to form DAPA. The …
Process for Recovering Polypeptides that Unfold Reversibly from a Polypeptide Repertoire
LS Jespers, PC Jones, HJK Famm… - US Patent App. 10 …, 2009 - Google Patents
The invention relates to polypeptides that unfold reversibly (eg, unfolds when heated and
refolds when cooled), to repertoires containing polypeptides that unfold reversibly and to
libraries that contain polypeptides that unfold reversibly or nucleic acids that encode …
refolds when cooled), to repertoires containing polypeptides that unfold reversibly and to
libraries that contain polypeptides that unfold reversibly or nucleic acids that encode …