Conjoined Hemoglobins. Loss of Cooperativity and Protein−Protein Interactions
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Bibliographic record
Abstract
Hemoglobin cross-linked as a bis(isophthalamide) of the epsilon-amino groups of lysine 82 of each beta-subunit binds and releases oxygen with a Hill coefficient indicative of cooperative oxygen binding (typically approximately 2.0). However, connecting two such cross-linked tetramers with a relatively short covalent linkage produces cross-linked bis-tetramers that bind oxygen with Hill coefficients near unity. To separate the effect of the linkages from the effects of protein-protein interactions in the conjoined proteins, reagents (1 and 2) were used to produce bis-tetramers (A and B). These have a considerably greater distance between cross-linked tetramers than earlier examples. Yet, the bis-tetramers (A and B) bind oxygen with minimal cooperativity (n(50) = 1.4, 1.2). To assess the effect of the linkage itself, cross-linked tetramers (Cand D) were prepared from reactions with the same reagents. These bind oxygen with cooperativity similar to that of cross-linked tetramers without the extended chain (C, n(50) = 2.0; D, n(50) = 1.8). Other tetramers (E and F) with flexible, saturated hydrocarbon appendages were also prepared. These also showed cooperativity in oxygen binding (E, n(50) = 1.7; F, n(50) = 1.8) despite their high degree of hydrophobicity. Thus, the intertetrameric linkages themselves do not induce the loss of cooperativity, leading to the conclusion that solution effects of the tetramers upon one another are the source of the decline in cooperativity: protein-protein interactions are most significant in disrupting the cooperativity of the bis-tetramers, regardless of the span or composition of the linker. This suggests that effects of oligomerization of hemoglobin within red cell substitutes should be considered in terms of such interactions.
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Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it