Insulin Aspart Precursor

Partition coefficient

Link to relevant study record(s)

Reference

Reference 1

Endpoint:

partition coefficient

Type of information:

read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

key study

Reason / purpose for cross-reference:

read-across source

Key result

Type:

log Pow

Partition coefficient:

0.4

pH:

ca. 7.9

Remarks on result:

not measured/tested

Remarks:

estimated values

Conclusions:

The partition coefficient of insulin aspart precurser (T) at 20 °C was estimated to 0.4

Executive summary:

The partition coefficient of octanol/water (Pow) of target substance insulin aspart precurser, is based on read across to MI3 (S2). The partition coefficient of MI3 was estimated from the water solubility (for MI3 and the n-octanol solubility (for insulin). The partition coefficient of insulin aspart precurser (T) at 20 °C was estimated to 0.4

Reference 2

Endpoint:

partition coefficient

Type of information:

calculation (if not (Q)SAR)

Adequacy of study:

weight of evidence

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

data from handbook or collection of data

Principles of method if other than guideline:

The partition coefficient octanol/water (Pow) has not been determined experimentally, but has been estimated from the water solubility (for MI3) and the n-octanol solubility (for insulin)

Key result

Type:

Pow

Partition coefficient:

ca. 0.4

Temp.:

20 °C

pH:

ca. 7.9

Conclusions:

The partition coefficient (pow) of MI3 (S2) at 20 °C is 0.4

Executive summary:

The partition coefficient of octanol/water (Pow) of MI3 was estimated from the water solubility (for MI3 and the n-octanol solubility (for insulin)   The insulin precursor MI3 is a proteinaceous material with 54 amino acid residues; MW ~ 5800 d. The water solubility of proteinaceous materials is generally low and depends on the molecules tertiary structure, i.e. how many hydrophilic groups that are present at the molecules surface. Furthermore, the solubility depends on the pH, the solubility being lowest at the isoelectric point. The water molecules associate with the hydrophilic groups at the surface and in this way may solubilise the molecule.   In general, proteinaceous materials are not very soluble in organic solvents. In the case of n-octanol the hydroxyl group will associate with the hydrophilic groups at the molecules surface in the same way as water, but the affinity will be lower. The lipophilic end of n-octanol may stick into lipophilic areas of the molecules surface leaving the hydrophilic end out in the solvent (n-octanol). At the isoelectric point the solubility in n-octanol is estimated to be maximum. The interactions of the solvents (water and n-octanol) with the solute molecule (MI3) will change the solubility - probably enhance it a little, because n-octanol is somewhat soluble in water (4.5 mM) and water is somewhat soluble in n-octanol (2.3 mM). Apart from these low soluble amounts in water and n-octanol, the proteinaceous material will sediment below the water phase or possibly be located at the interface between the two phases.The solubility in water of MI3 is approx. 400 mg/L and pH in the solution is approx. 7.9. The solubility of insulin in n-octanol is 1000 mg/L. The partition coefficient of MI3 (S2) at 20 °C was estimated to 0.4

Description of key information

Data on target substance not available. Thus, read-across has been applied using data from source substance (S2).

As can be seen from the molecular structure (see attached document in section 13) the target substance is a small protein consisting of 59 amino acids have at least 49 amino acids in common with the source substances (consisting of 50-53 amino acids) and having very identical amino acid sequences. Based on these structural similarities very similar physical chemical properties would be expected. This is further documented by the results from physical chemical guideline testing for S2 and S3 where the test results found for melting point, boiling point, flammability, self-ignition, and explosion were identical.

Additional information

The partition coefficient octanol/water (Pow) has not been determined experimentally, but has been estimated from the water solubility (for MI3) and the n-octanol solubility (for insulin)  The insulin precursor MI3 is a proteinaceous material with 54 amino acid residues; MW ~ 5800 d. The water solubility of proteinaceous materials is generally low and depends on the molecules tertiary structure, i.e. how many hydrophilic groups that are present at the molecules surface. Furthermore, the solubility depends on the pH, the solubility being lowest at the isoelectric point. The water molecules associate with the hydrophilic groups at the surface and in this way may solubilise the molecule.  In general, proteinaceous materials are not very soluble in organic solvents. In the case of n-octanol the hydroxyl group will associate with the hydrophilic groups at the molecules surface in the same way as water, but the affinity will be lower. The lipophilic end of n-octanol may stick into lipophilic areas of the molecules surface leaving the hydrophilic end out in the solvent (n-octanol). At the isoelectric point the solubility in n-octanol is estimated to be maximum.  The interactions of the solvents (water and n-octanol) with the solute molecule (MI3) will change the solubility - probably enhance it a little, because n-octanol is somewhat soluble in water (4.5 mM) and water is somewhat soluble in n-octanol (2.3 mM). Apart from these low soluble amounts in water and n-octanol, the proteinaceous material will sediment below the water phase or possibly be located at the interface between the two phases.The solubility in water of MI3 is approx. 400 mg/L and pH in the solution is approx. 7.9. The solubility of insulin in n-octanol is 1000 mg/L (Matsuura J, Powers ME, Manning MC, Shefter I. Structure and stability of insulin dissolved in 1-octanol. J Am Chem Soc 1993: 115(4); 1261-4). On this basis, Pow for MI3 may be estimated to approx. 2.5 (1000 / 400) or logPow ~ 0.4. Result:     LogPow = approximately 0.4 (estimated).

Therefore, the same conclusion for the target substance (Insulin Aspart Precursor) applies justified by the read-across hypothesis.