Kinetics of Insulin-like Growth Factor II (IGF-II) Interaction with Domain 11 of the Human IGF-II/Mannose 6-phosphate Receptor: Function of CD and AB Loop Solvent-exposed Residues

Zaccheo, Oliver; Prince, Stuart; Miller, David M.; Williams, Christopher; Kemp, C. Fred; Brown, James; Jones, E Y; Catto, Lucy E.; Crump, Matthew P.; Hassan, A. Bassim

doi:10.1016/j.jmb.2006.03.046

Cited by 28 publications

(50 citation statements)

References 75 publications

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“…Recombinant human IGF-I and IGF-II were from GroPep (Adelaide, South Australia, Australia). I1572A proteins were produced in Pichia Pastoris as described previously (44). Briefly, stable transformants were cultured at 300 rpm in 200 mL BMGY medium overnight at 30jC, then pelleted, and transferred to 200 mL BMMY medium for 3 days with 1% methanol added daily.…”

Section: Methodsmentioning

confidence: 99%

“…In addition, AB loop residues seem to act as second sphere residues that stabilize the interaction (44). Moreover, mutation of E1544 to alanine, lysine, arginine, and histidine significantly enhanced the affinity of domain 11 to IGF-II (44).…”

Section: Introductionmentioning

confidence: 99%

“…The former binding cleft volume (400 Å 3 ) is formed by loops AB, CD, and FG (42). Mutation of the solvent-exposed residues in this region (AB loop: Y1542, S1543, and G1546; CD loop: F1567, G1568, T1570, and I1572; and FG loop: S1596, P1597, and P1599) followed by real-time analysis of affinity has led to the identification of CD loop residues as essential for the initial hydrophobic docking with IGF-II (44). In addition, AB loop residues seem to act as second sphere residues that stabilize the interaction (44).…”

Section: Introductionmentioning

confidence: 99%

“…Mutation of the solvent-exposed residues in this region (AB loop: Y1542, S1543, and G1546; CD loop: F1567, G1568, T1570, and I1572; and FG loop: S1596, P1597, and P1599) followed by real-time analysis of affinity has led to the identification of CD loop residues as essential for the initial hydrophobic docking with IGF-II (44). In addition, AB loop residues seem to act as second sphere residues that stabilize the interaction (44). Moreover, mutation of E1544 to alanine, lysine, arginine, and histidine significantly enhanced the affinity of domain 11 to IGF-II (44).…”

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Functional evaluation of novel soluble insulin-like growth factor (IGF)-II–specific ligand traps based on modified domain 11 of the human IGF2 receptor

Prince¹,

Foulstone²,

Zaccheo³

et al. 2007

Molecular Cancer Therapeutics

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Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Functional evaluation of novel soluble insulin-like growth factor (IGF)-II–specific ligand traps based on modified domain 11 of the human IGF2 receptor

Prince¹,

Foulstone²,

Zaccheo³

et al. 2007

Molecular Cancer Therapeutics

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“…CIM6PR also mediates the endocytosis of extracellular ligands such as insulin-like growth factor 2 (IGF2), retinoic acid and M6P-containing proteins. [146][147][148] An endothelial cell monolayer associated with pericytes and astrocytes, known as the BBB, separates the blood from the cerebral parenchyma and prevents the penetration of drugs into the central nervous system. This barrier is characterized by tight intercellular junctions.…”

Section: Mannose Derivatesmentioning

confidence: 99%

Toward a magic or imaginary bullet? Ligands for drug targeting to cancer cells: principles, hopes, and challenges

Toporkiewicz¹,

Meissner²,

Matusewicz³

et al. 2015

IJN

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There are many problems directly correlated with the systemic administration of drugs and how they reach their target site. Targeting promises to be a hopeful strategy as an improved means of drug delivery, with reduced toxicity and minimal adverse side effects. Targeting exploits the high affinity of cell-surface-targeted ligands, either directly or as carriers for a drug, for specific retention and uptake by the targeted diseased cells. One of the most important parameters which should be taken into consideration in the selection of an appropriate ligand for targeting is the binding affinity ( K D ). In this review we focus on the importance of binding affinities of monoclonal antibodies, antibody derivatives, peptides, aptamers, DARPins, and small targeting molecules in the process of selection of the most suitable ligand for targeting of nanoparticles. In order to provide a critical comparison between these various options, we have also assessed each technology format across a range of parameters such as molecular size, immunogenicity, costs of production, clinical profiles, and examples of the level of selectivity and toxicity of each. Wherever possible, we have also assessed how incorporating such a targeted approach compares with, or is superior to, original treatments.

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Igf2 pathway dependency of the Trp53 developmental and tumour phenotypes

et al. 2012

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Insulin-like growth factor 2 (IGF2) and the transformation related protein 53 (Trp53) are potent regulators of cell growth and metabolism in development and cancer. In vitro evidence suggests several mechanistic pathway interactions. Here, we tested whether loss of function of p53 leads to IGF2 ligand pathway dependency in vivo. Developmental lethality occurred in p53 homozygote null mice that lacked the paternal expressed allele of imprinted Igf2. Further lethality due to post-natal lung haemorrhage occurred in female progeny with Igf2 paternal null allele only if derived from double heterozygote null fathers, and was associated with a specific gene expression signature. Conditional deletion of Igf2fl/fl attenuated the rapid tumour onset promoted by homozygous deletion of p53fl/fl. Accelerated carcinoma and sarcoma tumour formation in p53+/− females with bi-allelic Igf2 expression was associated with reductions in p53 loss of heterozygosity and apoptosis. Igf2 genetic dependency of the p53 null phenotype during development and tumour formation suggests that targeting the IGF2 pathway may be useful in the prevention and treatment of human tumours with a disrupted Trp53 pathway.

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Kinetics of Insulin-like Growth Factor II (IGF-II) Interaction with Domain 11 of the Human IGF-II/Mannose 6-phosphate Receptor: Function of CD and AB Loop Solvent-exposed Residues

Cited by 28 publications

References 75 publications

Functional evaluation of novel soluble insulin-like growth factor (IGF)-II–specific ligand traps based on modified domain 11 of the human IGF2 receptor

Functional evaluation of novel soluble insulin-like growth factor (IGF)-II–specific ligand traps based on modified domain 11 of the human IGF2 receptor

Toward a magic or imaginary bullet? Ligands for drug targeting to cancer cells: principles, hopes, and challenges

Igf2 pathway dependency of the Trp53 developmental and tumour phenotypes

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